Skip to main content

Advertisement

SpringerLink
Log in

Tumor necrosis factor alpha and interleukin-1 beta levels in cerebrospinal fluid examination for the diagnosis of ventriculoperitoneal shunt-related ventriculitis

  • Original Article
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

Ventriculitis is known to develop after chronic inflammation and bacterial invasion of the ventricular surface with a recurrence of shunt infections. The aim of this study is to evaluate the diagnostic value of elevation in cerebrospinal fluid (CSF) interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) together with CSF culture and laboratory test results in the diagnosis of ventriculoperitoneal (VP) shunt-related ventriculitis, which is known to be more problematic than conventional shunt infection.

Methods

The study included a total of 34 patients with a VP shunt due to hydrocephalus, who presented with a headache, fever, and shunt infection at the Emergency Department and had a pre-diagnosis of ventriculitis. Nineteen patients were diagnosed with shunt-related infection or ventriculitis using the CSF obtained from the shunt pump. The IL-1β and TNF-α levels from the CSF samples of all patients were measured using the Micro ELISA immunoassay method.

Results

CSF direct microscopic observation revealed that the mean cell count, IL-1β level, CRP level, and blood leukocyte level were higher in patients with ventriculitis compared to those diagnosed with shunt infection (p = 0.02, p = 0.009, p = 0.004, and p = 0.009, respectively). The probability of predicting positive culture outcome was 92.7% with 90.9% sensitivity and 82.6% specificity when IL-1β values exceeded 4.0 pg/ml. TNF-α values did not show a significant, reliable pattern compared to IL-1β.

Conclusions

IL-1β is a reliable parameter which shall be used in the diagnosis of ventriculitis by predicting positive culture outcome with high sensitivity and specificity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Asi-Bautista MC, Heidemann SM, Meert KL, Canady AI, Sarnaik AP (1997) Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 concentrations in cerebrospinal fluid predict ventriculoperitoneal shunt infection. Crit Care Med 25:1713–1716

    Article  CAS  PubMed  Google Scholar 

  2. Barichello T, dos Santos I, Savi GD, Simões LR, Silvestre T, Comim CM, Sachs D, Teixeira MM, Teixeira AL, Quevedo J (2010) TNF-α, IL-1β, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae. J Neuroimmunol 221:42–45. https://doi.org/10.1016/j.jneuroim.2010.02.009

    Article  CAS  PubMed  Google Scholar 

  3. Beer R, Lackner P, Pfausler B, Schmutzhard E (2008) Nosocomial ventriculitis and meningitis in neurocritical care patients. J Neurol 255:1617–1624. https://doi.org/10.1007/s00415-008-0059-8

    Article  CAS  PubMed  Google Scholar 

  4. Belogurov AA, Ivanova OM, Lomakin YA, Ziganshin RH, Vaskina MI, Knorre VD, Klimova EA, Gabibov AG, Ivanov VT, Govorun VM (2016) Mediators and biomarkers of inflammation in meningitis: cytokine and peptidome profiling of cerebrospinal fluid. Biochemistry (Mosc) 81:1293–1302. https://doi.org/10.1134/S0006297916110079

    Article  CAS  Google Scholar 

  5. Boeer K, Vogelsang H, Deufel T, Pfister W, Kiehntopf M (2011) Immediate diagnosis of ventriculits: evaluation of parameters independent of microbiological culture. Acta Neurochir 153:1797–1805. https://doi.org/10.1007/s00701-011-1079-1

    Article  PubMed  Google Scholar 

  6. Chen K, Wu Y, Wang Q, Wang J, Li X, Zhao Z, Zhou J (2015) The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy. J Crit Care 30:218.e1–218.e5. https://doi.org/10.1016/j.jcrc.2014.09.020

    Article  CAS  Google Scholar 

  7. Cuchacovich M, Bueno D, Carvajal R, Bravo N, Aguillón JC, Catalán D, Soto L (2014) Clinical parameters and biomarkers for anti-TNF treatment prognosis in rheumatoid arthritis patients. Clin Rheumatol 33:1707–1714. https://doi.org/10.1007/s10067-014-2756-2

    Article  PubMed  Google Scholar 

  8. Fida NM, Al-Mughales J, Farouq M (2006) Interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha levels in children with sepsis and meningitis. Pediatr Int 48:118–124. https://doi.org/10.1111/j.1442-200X.2006.02152.x

    Article  CAS  PubMed  Google Scholar 

  9. Friedrich EE, Sun LT, Natesan S, Zamora DO, Christy RJ, Washburn NR (2014) Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns. J Biomed Mater Res Part A 102:1527–1536. https://doi.org/10.1002/jbm.a.34829

    Article  CAS  Google Scholar 

  10. Gordon M, Ramirez P, Soriano A, Palomo M, Lopez-Ferraz C, Villarreal E, Meseguer S, Gomez MD, Folgado C, Bonastre J (2014) Diagnosing external ventricular drain-related ventriculitis by means of local inflammatory response: soluble triggering receptor expressed on myeloid cells-1. Crit Care 18:567. https://doi.org/10.1186/s13054-014-0567-0

    Article  PubMed  PubMed Central  Google Scholar 

  11. Grandgirard D, Gäumann R, Coulibaly B, Dangy J-P, Sie A, Junghanss T, Schudel H, Pluschke G, Leib SL (2013) The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis. Mediat Inflamm 2013:312476. doi: https://doi.org/10.1155/2013/312476, 1, 12

  12. Handa S (1992) Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis. Kurume Med J 39:257–265

    Article  CAS  PubMed  Google Scholar 

  13. Krebs VLJ, Okay TS, Okay Y, Vaz FAC (2005) Tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in the cerebrospinal fluid of newborn with meningitis. Arq Neuropsiquiatr 63:7–13

    Article  PubMed  Google Scholar 

  14. Laborada G, Cruz F, Nesin M (2005) Serial cytokine profiles in shunt-related ventriculitis treated with intraventricular vancomycin. Chemotherapy 51:363–365. https://doi.org/10.1159/000088963

    Article  CAS  PubMed  Google Scholar 

  15. Lifshutz JI, Johnson WD (2001) History of hydrocephalus and its treatments. Neurosurg Focus:11:1–11:5. https://doi.org/10.3171/foc.2001.11.2.2

  16. López-Cortés LF, Marquez-Arbizu R, Jimenez-Jimenez LM, Jimenez-Mejías E, Caballero-Granado FJ, Rey-Romero C, Polaina M, Pachón J (2000) Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients. Crit Care Med 28:215–219

    Article  PubMed  Google Scholar 

  17. Morris A, Low DE (1999) Nosocomial bacterial meningitis, including central nervous system shunt infections. Infect Dis Clin N Am 13:735–750

    Article  CAS  Google Scholar 

  18. Mukai AO, Krebs VLJ, Bertoli CJ, Okay TS (2006) TNF-alpha and IL-6 in the diagnosis of bacterial and aseptic meningitis in children. Pediatr Neurol 34:25–29. https://doi.org/10.1016/j.pediatrneurol.2005.06.003

    Article  PubMed  Google Scholar 

  19. Mustafa MM, Mertsola J, Ramilo O, Sáez-Llorens X, Risser RC, McCracken GH (1989) Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy. J Infect Dis 160:891–895

    Article  CAS  PubMed  Google Scholar 

  20. Panato APR, Tomasi LT, Simon CS, Madeira K, Simoes LR, Medeiros LR, Barichello T, Rosa MI (2014) Meta-analysis identifies tumor necrosis factor-alpha and interleukin-1 beta as diagnostic biomarkers for bacterial and aseptic meningitis. Curr Neurovasc Res 11:340–348

    Article  CAS  PubMed  Google Scholar 

  21. Prasad R, Kapoor R, Srivastava R, Mishra OP, Singh TB (2014) Cerebrospinal fluid TNF-α, IL-6, and IL-8 in children with bacterial meningitis. Pediatr Neurol 50:60–65. https://doi.org/10.1016/j.pediatrneurol.2013.08.016

    Article  PubMed  Google Scholar 

  22. Ramilo O, Sáez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, Yoshinaga M, Ohkawara S, Nariuchi H, McCracken GH (1990) Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med 172:497–507

    Article  CAS  PubMed  Google Scholar 

  23. Sampedro MF, Patel R (2007) Infections associated with long-term prosthetic devices. Infect Dis Clin N Am 21:785–819. https://doi.org/10.1016/j.idc.2007.07.001

    Article  Google Scholar 

  24. Scheithauer S, Bürgel U, Ryang Y-M, Haase G, Schiefer J, Koch S, Häfner H, Lemmen S (2009) Prospective surveillance of drain associated meningitis/ventriculitis in a neurosurgery and neurological intensive care unit. J Neurol Neurosurg Psychiatry 80:1381–1385. https://doi.org/10.1136/jnnp.2008.165357

    Article  CAS  PubMed  Google Scholar 

  25. Schoenbaum SC, Gardner P, Shillito J (1975) Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations, and therapy. J Infect Dis 131:543–552

    Article  CAS  PubMed  Google Scholar 

  26. Schuhmann MU, Ostrowski KR, Draper EJ, Chu J-W, Ham SD, Sood S, McAllister JP (2005) The value of C-reactive protein in the management of shunt infections. J Neurosurg 103:223–230. https://doi.org/10.3171/ped.2005.103.3.0223

    Article  PubMed  Google Scholar 

  27. Srinivasan L, Kilpatrick L, Shah SS, Abbasi S, Harris MC (2016) Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants. Pediatr Res 80:566–572. https://doi.org/10.1038/pr.2016.117

    Article  CAS  PubMed  Google Scholar 

  28. Sulik A, Kroten A, Wojtkowska M, Oldak E (2014) Increased levels of cytokines in cerebrospinal fluid of children with aseptic meningitis caused by mumps virus and echovirus 30. Scand J Immunol 79:68–72. https://doi.org/10.1111/sji.12131

    Article  CAS  PubMed  Google Scholar 

  29. Tabuchi S, Kadowaki M (2015) Neuroendoscopic surgery for ventriculitis and hydrocephalus after shunt infection and malfunction: preliminary report of a new strategy. Asian J Endosc Surg 8:180–184. https://doi.org/10.1111/ases.12162

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tang RB, Lee BH, Chung RL, Chen SJ, Wong TT (2001) Interleukin-1beta and tumor necrosis factor-alpha in cerebrospinal fluid of children with bacterial meningitis. Childs Nerv Syst 17:453–456

    Article  CAS  PubMed  Google Scholar 

  31. Taskin E, Turgut M, Kilic M, Akbulut H, Aygun AD (2004) Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis. Mediat Inflamm 13:269–273. https://doi.org/10.1080/09629350400003084

    Article  CAS  Google Scholar 

  32. Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, van de Beek D, Bleck TP, Garton HJL, Zunt JR (2017) 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis 64:e34–e65. https://doi.org/10.1093/cid/ciw861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vanaclocha V, Sáiz-Sapena N, Leiva J (1996) Shunt malfunction in relation to shunt infection. Acta Neurochir 138:829–834

    Article  CAS  PubMed  Google Scholar 

  34. (2000) The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy Br J Neurosurg 14:7–12

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Adana City Training Research Hospital, Adana, Turkey

    Semih K. Olguner, Ali Arslan, Emre Bilgin & Ali Ihsan Okten

  2. Department of Neurosurgery, Cukurova University of Medical School, Adana, Turkey

    Bulent Boyar & Tahsin Erman

  3. Pediatric Infectious Disease Department, Cukurova University of Medical School, Adana, Turkey

    Derya Alabaz

  4. Department of Neurosurgery, Medical Park Hospital, Gaziantep, Turkey

    Kadir Oktay

Authors
  1. Semih K. Olguner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bulent Boyar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Derya Alabaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tahsin Erman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kadir Oktay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emre Bilgin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ali Ihsan Okten
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Semih K. Olguner, Bulent Boyar, Derya Alabaz, and Tahsin Erman were involved in the study conception and design. Ali İhsan Okten, Ali Arslan, Emre Bilgin, and Kadir Oktay were responsible for the data analysis. All authors contributed to the discussion, interpreted the findings, helped write, reviewed/edited the manuscript for intellectual content, and read and approved the final manuscript.

Corresponding author

Correspondence to Semih K. Olguner.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Çukurova Medical Faculty. All participants provided informed consent.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olguner, S.K., Boyar, B., Alabaz, D. et al. Tumor necrosis factor alpha and interleukin-1 beta levels in cerebrospinal fluid examination for the diagnosis of ventriculoperitoneal shunt-related ventriculitis. Childs Nerv Syst 35, 629–636 (2019). https://doi.org/10.1007/s00381-019-04070-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-019-04070-x

Keywords

Search

Navigation