Skip to main content

International Infant Hydrocephalus Study: initial results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus

Abstract

Introduction

The IIHS is an international, prospective, multicenter study to compare endoscopic third ventriculostomy (ETV) and shunt in infants (<24 months old) with symptomatic triventricular hydrocephalus from aqueductal stensosis. Recruitment started in 2004, and here, we present the first results of IIHS.

Methods

IIHS utilized a prospective comprehensive cohort design, which contained both a randomized and a non-randomized arm. Patients received either an ETV or shunt, based on randomization or parental preference. Patients were followed prospectively for time to treatment failure, defined as the need for repeat CSF diversion procedure (shunt or ETV) or death due to hydrocephalus. Survival analysis was used to compare time to failure for ETV versus shunt. The trial was registered at clinicaltrials.gov (NCT00652470).

Results

A total of 158 patients met eligibility criteria (median age at surgery 3.6 months, IQR 1.6–6.6 months) across 27 centers in 4 continents. Since only 52 patients (32.9 %) were randomized, all 158 patients were analyzed together (115 ETV, 43 shunt). Actuarial success rates for ETV vs shunt at 3, 6, and 12 months were as follows: 68 vs 95 %, 66 vs 88 %, and 66 vs 83 %. The 6-month ETV success rate of 66 % was slightly higher than would have been predicted by the ETV Success Score (57 %).The hazard ratio for time to treatment failure favored shunt over ETV (3.17, 95 % CI 1.45–6.96, p = 0.004), after adjusting for age at surgery, history of previous hemorrhage or infection, continent, and randomization status. Patients younger than 6 months of age appeared to do relatively worse with ETV than older patients.

Conclusions

The IIHS has provided the first prospective direct comparison of ETV and shunt for infant hydrocephalus. These initial results suggest that shunting has a superior success rate compared to ETV, although the success rate for both was relatively high. This patient cohort continues to be followed, and we will await the results of the important primary outcome of health status at 5 years of age.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. O’Brien DF, Seghedoni A, Collins DR, et al. (2006) Is there an indication for ETV in young infants in aetiologies other than isolated aqueduct stenosis? Childs Nerv Syst 22:1565–1572

    Article  PubMed  Google Scholar 

  2. Constantini S, Sgouros S, Kulkarni A (2013) Neuroendoscopy in the youngest age group. 79:S23

  3. Fritsch MJ, Kienke S, Ankermann T, et al. (2005) Endoscopic third ventriculostomy in infants. J Neurosurg 103:50–53

    PubMed  Google Scholar 

  4. Balthasar AJ, Kort H, Cornips EM, et al. (2007) Analysis of the success and failure of endoscopic third ventriculostomy in infants less than 1 year of age. Childs Nerv Syst 23:151–155

    CAS  Article  PubMed  Google Scholar 

  5. Wagner W, Koch D (2005) Mechanisms of failure after endoscopic third ventriculostomy in young infants. J Neurosurg 103:43–49

    PubMed  Google Scholar 

  6. Gorayeb RP, Cavalheiro S, Zymberg ST (2004) Endoscopic third ventriculostomy in children younger than 1 year of age. J Neurosurg 100:427–429

    PubMed  Google Scholar 

  7. Javadpour M, Mallucci C, Brodbelt A, et al. (2001) The impact of endoscopic third ventriculostomy on the management of newly diagnosed hydrocephalus in infants. Pediatr Neurosurg 35:131–135

    CAS  Article  PubMed  Google Scholar 

  8. Baldauf J, Oertel J, Gaab MR, Schroeder HWS (2007) Endoscopic third ventriculostomy in children younger than 2 years of age. Childs Nerv Syst 23:623–626. doi:10.1007/s00381-007-0335-4

    Article  PubMed  Google Scholar 

  9. Drake JM, Kulkarni AV, Kestle J (2009) Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric patients: a decision analysis. Childs Nerv Syst 25:467–472. doi:10.1007/s00381-008-0761-y

    Article  PubMed  Google Scholar 

  10. Kulkarni AV, Hui S, Shams I, Donnelly R (2010) Quality of life in obstructive hydrocephalus: endoscopic third ventriculostomy compared to cerebrospinal fluid shunt. Childs Nerv Syst 26:75–79. doi:10.1007/s00381-009-0983-7

    Article  PubMed  Google Scholar 

  11. Rasul FT, Marcus HJ, Toma AK, et al. (2013) Is endoscopic third ventriculostomy superior to shunts in patients with non-communicating hydrocephalus? A systematic review and meta-analysis of the evidence. Acta Neurochir 155:883–889. doi:10.1007/s00701-013-1657-5

    CAS  Article  PubMed  Google Scholar 

  12. Kulkarni AV, Drake JM, Kestle JR, et al. (2010) Endoscopic third ventriculostomy vs cerebrospinal fluid shunt in the treatment of hydrocephalus in children: a propensity score-adjusted analysis. Neurosurgery 67:588–593. doi:10.1227/01.NEU.0000373199.79462.21

    Article  PubMed  Google Scholar 

  13. Kulkarni AV, Drake JM, Kestle JRW, et al. (2010) Predicting who will benefit from endoscopic third ventriculostomy compared with shunt insertion in childhood hydrocephalus using the ETV Success Score. J Neurosurg Pediatr 6:310–315. doi:10.3171/2010.8.PEDS103a

    Article  PubMed  Google Scholar 

  14. Kulkarni AV (2006) Questionnaire for assessing parents’ concerns about their child with hydrocephalus. Dev Med Child Neurol 48:108–113

    Article  PubMed  Google Scholar 

  15. Kulkarni AV (2007) Assessment of mother and father concern in childhood hydrocephalus. Qual Life Res 16:1501–1509. doi:10.1007/s11136-007-9258-5

    Article  PubMed  Google Scholar 

  16. Kulkarni AV, Shams I (2007) Quality of life in children with hydrocephalus: results from the Hospital for Sick Children, Toronto. J Neurosurg 107:358–364. doi:10.3171/PED-07/11/358

    PubMed  Google Scholar 

  17. Kulkarni AV, Cochrane DD, McNeely PD, Shams I (2008) Medical, social, and economic factors associated with health-related quality of life in Canadian children with hydrocephalus. J Pediatr 153:689–695. doi:10.1016/j.jpeds.2008.04.068

    Article  PubMed  Google Scholar 

  18. Kulkarni AV (2010) Quality of life in childhood hydrocephalus: a review. Childs Nerv Syst 26:737–743. doi:10.1007/s00381-010-1131-0

    Article  PubMed  Google Scholar 

  19. Kulkarni AV, Shams I, Cochrane DD, McNeely PD (2010) Quality of life after endoscopic third ventriculostomy and cerebrospinal fluid shunting: an adjusted multivariable analysis in a large cohort. J Neurosurg Pediatr 6:11–16. doi:10.3171/2010.3.PEDS09358

    Article  PubMed  Google Scholar 

  20. Sgouros S, Kulkharni AV, Constantini S (2006) The international infant hydrocephalus study: concept and rational. Childs Nerv Syst 22:338–345. doi:10.1007/s00381-005-1253-y

    CAS  Article  PubMed  Google Scholar 

  21. Feeny D, Furlong W, Boyle M, Torrance GW (1995) Multi-attribute health status classification systems. Health Util Index Pharmacoecon 7:490–502

    CAS  Google Scholar 

  22. Kulkarni AV, Drake JM, Mallucci CL, et al. (2009) Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus. J Pediatr. doi:10.1016/j.jpeds.2009.02.048

    PubMed Central  Google Scholar 

  23. Olschewski M, Schumacher M, Davis KB (1992) Analysis of randomized and nonrandomized patients in clinical trials using the comprehensive cohort follow-up study design. Control Clin Trials 13:226–239

    CAS  Article  PubMed  Google Scholar 

  24. Jones RF, Stening WA, Brydon M (1990) Endoscopic third ventriculostomy. Neurosurgery 26:82–86

    Article  Google Scholar 

  25. Drake JM, Kestle JR, Milner R, et al. (1998) Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus. Neurosurgery 43:294–295

    CAS  Article  PubMed  Google Scholar 

  26. Kulkarni AV, Riva-Cambrin J, Butler J, et al. (2013) Outcomes of CSF shunting in children: comparison of hydrocephalus clinical research network cohort with historical controls: clinical article. J Neurosurg Pediatr 12:334–338. doi:10.3171/2013.7.PEDS12637

    Article  PubMed  Google Scholar 

  27. Kestle J, Drake J, Milner R, et al. (2000) Long-term follow-up data from the shunt design trial. Pediatr Neurosurg 33:230–236

    CAS  Article  PubMed  Google Scholar 

  28. Furlanetti LL, Santos MV, De Oliveira RS (2013) The success of endoscopic third ventriculostomy in children: analysis of prognostic factors. Pediatr Neurosurg 48:352–359. doi:10.1159/000353619

    Article  Google Scholar 

  29. Kulkarni AV, Riva-Cambrin J, Browd SR (2011) Use of the ETV Success Score to explain the variation in reported endoscopic third ventriculostomy success rates among published case series of childhood hydrocephalus. J Neurosurg Pediatr 7:143–146. doi:10.3171/2010.11.PEDS10296

    Article  PubMed  Google Scholar 

  30. Naftel RP, Reed GT, Kulkarni AV, Wellons JC (2011) Evaluating the Children’s Hospital of Alabama endoscopic third ventriculostomy experience using the Endoscopic Third Ventriculostomy Success Score: an external validation study. J Neurosurg Pediatr 8:494–501. doi:10.3171/2011.8.PEDS1145

    Article  PubMed  Google Scholar 

  31. Breimer GE, Sival DA, Brusse-Keizer MGJ, Hoving EW (2013) An external validation of the ETVSS for both short-term and long-term predictive adequacy in 104 pediatric patients. Childs Nerv Syst 29:1305–1311. doi:10.1007/s00381-013-2122-8

    CAS  Article  PubMed  Google Scholar 

  32. García LG, López BR, Botella GI, et al. (2012) Endoscopic third ventriculostomy success score (ETVSS) predicting success in a series of 50 pediatric patients. are the outcomes of our patients predictable? Childs Nerv Syst 28:1157–1162. doi:10.1007/s00381-012-1836-3

    Article  PubMed  Google Scholar 

  33. Durnford AJ, Kirkham FJ, Mathad N, Sparrow OC (2011) Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus: validation of a success score that predicts long-term outcome. J Neurosurg Pediatr 8:489–493. doi:10.3171/2011.8.PEDS1166

    Article  PubMed  Google Scholar 

  34. Vogel TW, Bahuleyan B, Robinson S, Cohen AR (2013) The role of endoscopic third ventriculostomy in the treatment of hydrocephalus. J Neurosurg Pediatr 12:54–61. doi:10.3171/2013.4.PEDS12481

    Article  PubMed  Google Scholar 

  35. Azimi P, Mohammadi HR (2014) Predicting endoscopic third ventriculostomy success in childhood hydrocephalus: an artificial neural network analysis. J Neurosurg Pediatr 13:426–432. doi:10.3171/2013.12.PEDS13423

    Article  PubMed  Google Scholar 

  36. Kestle J, Milner R, Drake D (1999) An assessment of observer bias in the shunt design trial. Pediatr Neurosurg 30:57–61

    CAS  Article  PubMed  Google Scholar 

  37. Warf BC (2005) Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. J Neurosurg 103:475–481

    PubMed  Google Scholar 

  38. Warf BC, Tracy S, Mugamba J (2012) Long-term outcome for endoscopic third ventriculostomy alone or in combination with choroid plexus cauterization for congenital aqueductal stenosis in African infants. J Neurosurg Pediatr 10:108–111. doi:10.3171/2012.4.PEDS1253

    Article  PubMed  Google Scholar 

  39. Stone SSD, Warf BC (2014) Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment for infant hydrocephalus: a prospective North American series. J Neurosurg Pediatr 14:439–446. doi:10.3171/2014.7.PEDS14152

    Article  PubMed  Google Scholar 

  40. Kulkarni AV, Riva-Cambrin J, Browd SR, et al. (2014) Endoscopic third ventriculostomy and choroid plexus cauterization in infants with hydrocephalus: a retrospective Hydrocephalus Clinical Research Network study. J Neurosurg Pediatr 14:224–229. doi:10.3171/2014.6.PEDS13492

    Article  PubMed  Google Scholar 

  41. Chamiraju P, Bhatia S, Sandberg DI, Ragheb J (2014) Endoscopic third ventriculostomy and choroid plexus cauterization in posthemorrhagic hydrocephalus of prematurity. J Neurosurg Pediatr 13:433–439. doi:10.3171/2013.12.PEDS13219

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to extend special thanks to Adina Sherer, who ran the organizational logistics of this study and without whom the IIHS would not have been possible.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Shlomi Constantini.

Ethics declarations

Conflict of interest

The members of the Steering Committee have no conflicts of interest with respect to this work.

Additional information

See “Appendix” for full list of study investigators

Appendix: IIHS personnel

Appendix: IIHS personnel

Steering Committee: Shlomi Constantini (Principal Investigator), Spyros Sgouros, Abhaya V. Kulkarni

Consultant Neurologist: Yael Leitner

Data Safety Monitoring Committee: John RW Kestle (Chair), Douglas D Cochrane, Maurice Choux, Fleming Gjerris

Coordinating Administrator: Adina Sherer

Participating investigators (in parentheses are the number of eligible patients contributed to the study by each investigator)

Medical Center IIHS participants # of patients
Ankara, Turkey
Hacettepe University Hospital
Nejat Akalan, Burçak Bilginer (12)
Barcelona, Spain
Hospital Sant Joan de Deu
Ramon Navarro
(currently at Cleveland Clinic Abu Dhabi, UAE)
(7)
Belgrade, Serbia
Clinical Center of Serbia, Belgrade, Neurosurgery Division
Ljiljana Vujotic (8)
Berlin, Germany
Charité—Universitätsmedizin Berlin
Hannes Haberl, Ulrich-Wilhelm Thomale (4)
Birmingham, UK
Birminghan Children’s Hospital
Spyros Sgouros
(currently at “Mitera” Childrens Hospital)
(1)
Buenos Aires, Argentina
Hospital De Pediatria Prof. Dr. J.P. Garrahan
Graciela Zúccaro, Roberto Jaimovitch (21)
Chicago, USA
The University of Chicago Comer Children’s Hospital
David Frim, Lori Loftis (3)
Dallas, USA
Children’s Medical Center of Dallas
Dale M. Swift, Brian Robertson, Lynn Gargan (6)
Debrecen, Hungary
University of Debrecen, Clinical Center, Department of Neurosurgery
László Bognár, László Novák, Georgina Cseke (5)
Genova, Italy
Giannina Gaslini Hospital, Gaslini Children Institute
Armando Cama, Giuseppe Marcello Ravegnani (3)
Giessen/Leipzig
University Hospital Gießen and Marburg
Matthias Preuß
Currently at University Hospital Leipzig
(4)
Greifswald, Germany
Ernst-Moritz-Arndt-Universität Klinik für Neurochirurgie
Henry W. Schroeder, Michael Fritsch, Joerg Baldauf (2)
Katowice, Poland Medical University of Silesia Marek Mandera, Jerzy Luszawski, Patrycja Skorupka (9)
Liverpool, UK
Alder Hey Children’s Hospital
Conor Mallucci, Dawn Williams (4)
Lodz, Poland
Polish Mother’s Memorial Hospital, Research Institute
Krzysztof Zakrzewski, Emilia Nowoslawska (2)
Lucknow (KGMC), India
CSM Medical University (KGMC)
Chhitij Srivastava (4)
Lucknow (SGPGI), India
Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI)
Ashok K. Mahapatra, Raj Kumar, Rabi Narayan Sahu (8)
Moscow, Russia
Burdenko Neurosurgical Institute
Armen G. Melikian (Армен Меликян), Anton Korshunov (Антон Евгеньевич Коршунов), Anna Galstyan (Анна Галстян) (11)
New Delhi, India
All India Institute of Medical Sciences
Ashish Suri, Deepak Gupta (12)
Nijmegen, The Netherlands
Radboud University Medical Center
J. André Grotenhuis, Erik J. van Lindert (9)
Nova Lima, Brazil
Neurocirurgia Infantil, Biocor Instituto
José Aloysio da Costa Val (5)
Rome, Italy
Pediatric Neurosurgery, Policlinico Universitario “A. Gemelli”
Concezio Di Rocco, Gianpiero Tamburrini (4)
São Paulo, Brazil
Escola Paulista de Medicina, UNIFESP
Samuel Tau Zymberg, Sergio Cavalheiro (3)
Shanghai, China
Xinhua Hospital, Shanghai JiaoTong University School of Medicine
Ma Jie, Jiang Feng (3)
Tel Aviv, Israel
Dana Children’s Hospital, Tel Aviv Medical Center
Shlomi Constantini, Orna Friedman (20)
Toronto, Canada
Hospital for Sick Children
Abhaya V. Kulkarni (5)
Warsaw, Poland
Children’s Memorial Health Institute
Marcin Roszkowski, Slawomir Barszcz (7)

The following centers (and investigators) participated in the IIHS, but did not enroll any patients: Baltimore, MD, USA (George Jallo); Gainesville, FL, USA (David W. Pincus, Bridget Richter); Kiel, Germany (HM Mehdorn, Susan Schultka); London, ON, Canada (Sandrine de Ribaupierre); London, UK (Dominic Thompson, Silvia Gatscher); Mainz, Germany (Wolfgang Wagner, Dorothee Koch); Reggio Calabria, Italy (Saverio Cipri, Claudio Zaccone); Winnipeg, MB, Canada (Patrick McDonald)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kulkarni, A.V., Sgouros, S., Constantini, S. et al. International Infant Hydrocephalus Study: initial results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus. Childs Nerv Syst 32, 1039–1048 (2016). https://doi.org/10.1007/s00381-016-3095-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-016-3095-1

Keywords

  • Endoscopic third ventriculostomy
  • Triventricular hydrocephalus
  • ETV Success Score