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.
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References
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
Constantini S, Sgouros S, Kulkarni A (2013) Neuroendoscopy in the youngest age group. 79:S23
Fritsch MJ, Kienke S, Ankermann T, et al. (2005) Endoscopic third ventriculostomy in infants. J Neurosurg 103:50–53
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
Wagner W, Koch D (2005) Mechanisms of failure after endoscopic third ventriculostomy in young infants. J Neurosurg 103:43–49
Gorayeb RP, Cavalheiro S, Zymberg ST (2004) Endoscopic third ventriculostomy in children younger than 1 year of age. J Neurosurg 100:427–429
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
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
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
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
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
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
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
Kulkarni AV (2006) Questionnaire for assessing parents’ concerns about their child with hydrocephalus. Dev Med Child Neurol 48:108–113
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
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
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
Kulkarni AV (2010) Quality of life in childhood hydrocephalus: a review. Childs Nerv Syst 26:737–743. doi:10.1007/s00381-010-1131-0
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
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
Feeny D, Furlong W, Boyle M, Torrance GW (1995) Multi-attribute health status classification systems. Health Util Index Pharmacoecon 7:490–502
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
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
Jones RF, Stening WA, Brydon M (1990) Endoscopic third ventriculostomy. Neurosurgery 26:82–86
Drake JM, Kestle JR, Milner R, et al. (1998) Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus. Neurosurgery 43:294–295
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
Kestle J, Drake J, Milner R, et al. (2000) Long-term follow-up data from the shunt design trial. Pediatr Neurosurg 33:230–236
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
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
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
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
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
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
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
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
Kestle J, Milner R, Drake D (1999) An assessment of observer bias in the shunt design trial. Pediatr Neurosurg 30:57–61
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
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
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
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
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
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.
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The members of the Steering Committee have no conflicts of interest with respect to this work.
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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)
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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
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DOI: https://doi.org/10.1007/s00381-016-3095-1