J Neurosurg Pediatrics 12:334–338, 2013 ©AANS, 2013
Outcomes of CSF shunting in children: comparison of Hydrocephalus Clinical Research Network cohort with historical controls Clinical article Abhaya V. Kulkarni, M.D., Ph.D.,1 Jay Riva-Cambrin, M.D., M.Sc., 2 Jerry Butler, M.S., 2 Samuel R. Browd, M.D., Ph.D., 3 James M. Drake, M.B.B.Ch., M.Sc.,1 Richard Holubkov, Ph.D., 2 John R. W. Kestle, M.D., M.Sc., 2 David D. Limbrick, M.D., Ph.D., 4 Tamara D. Simon, M.D., M.S.P.H., 3 Mandeep S. Tamber, M.D., Ph.D., 5 John C. Wellons III, M.D., M.S.P.H., 6 and William E. Whitehead, M.D., M.P.H.,7 for the Hydrocephalus Clinical Research Network Hospital for Sick Children, University of Toronto, Ontario, Canada; 2Primary Children’s Medical Center, Salt Lake City, Utah; 3Seattle Children’s Hospital, University of Washington, Seattle, Washington; 4St. Louis Children’s Hospital, St. Louis, Missouri; 5Children’s Hospital of Pittsburgh, Pennsylvania; 6Vanderbilt University, Nashville, Tennessee; and 7Texas Children’s Hospital, Houston, Texas 1
Object. The Hydrocephalus Clinical Research Network (HCRN), which comprises 7 pediatric neurosurgical centers in North America, provides a unique multicenter assessment of the current outcomes of CSF shunting in nonselected patients. The authors present the initial results for this cohort and compare them with results from prospective multicenter trials performed in the 1990s. Methods. Analysis was restricted to patients with newly diagnosed hydrocephalus undergoing shunting for the first time. Detailed perioperative data from 2008 through 2012 for all HCRN centers were prospectively collected and centrally stored by trained research coordinators. Historical control data were obtained from the Shunt Design Trial (1993–1995) and the Endoscopic Shunt Insertion Trial (1996–1999). The primary outcome was time to first shunt failure, which was determined by using Cox regression survival analysis. Results. Mean age of the 1184 patients in the HCRN cohort was older than mean age of the 720 patients in the historical cohort (2.51 years vs 1.60 years, p < 0.0001). The distribution of etiologies differed (p < 0.0001, chi-square test); more tumors and fewer myelomeningoceles caused the hydrocephalus in the HCRN cohort patients. The hazard ratio for first shunt failure significantly favored the HCRN cohort, even after the model was adjusted for the prognostic effects of age and etiology (adjusted HR 0.82, 95% CI 0.69–0.96). Conclusions. Current outcomes of shunting in general pediatric neurosurgery practice have improved over those from the 1990s, although the reasons remain unclear. (http://thejns.org/doi/abs/10.3171/2013.7.PEDS12637)
Key Words • historical cohort • hydrocephalus • pediatric • shunt
A
CSF shunting has been the most widely used treatment for hydrocephalus over the past half century, it is unclear whether outcomes of shunting have improved dramatically over time. Since 2006, the HCRN, a multicenter network of pediatric neurosurgical institutions, has been dedicated to collecting high-quality data on the outcomes of hydrocephalus lthough
Abbreviation used in this paper: HCRN = Hydrocephalus Clinical Research Network.
334
treatment in children.6,11,13 The HCRN currently comprises 7 centers in North America and provides a unique opportunity for assessing the current outcomes of CSF shunting in nonselected patients. The objective of this study was to present the initial results for these patients (HCRN cohort) and compare them with historical data from prospective multicenter trials performed in the This article contains some figures that are displayed in color online but in black-and-white in the print edition.
J Neurosurg: Pediatrics / Volume 12 / October 2013
Outcomes of CSF shunting 1990s (historical cohort).1,3,5 The primary aim was to determine whether the outcomes of CSF shunt failures among children have changed over the past decade.
Methods Population
All patients were 19 years of age or younger; had newly diagnosed, previously untreated hydrocephalus; and were treated by pediatric neurosurgeons at specialized centers. Patients in the HCRN cohort were treated at 1 of 7 network centers (Children’s Hospital of Alabama, Birmingham, AL; Primary Children’s Hospital, Salt Lake City, UT; Seattle Children’s Hospital, Seattle, WA; Children’s Hospital of Pittsburgh, PA; St. Louis Children’s Hospital, St. Louis, MO; Texas Children’s Hospital, Houston, TX; Sick Kids Hospital (Hospital for Sick Children), Toronto, Canada). As part of the HCRN ongoing core data project, which began in April 2008, trained, dedicated research coordinators at each center collect data for all patients undergoing hydrocephalus-related surgery. Data are stored centrally and securely at the Data Coordinating Center in Salt Lake City. To ensure data accuracy and timeliness, standardized audits of data accuracy are performed regularly. Patients in the historical cohort had participated in 1 of 2 prospective trials: the Shunt Design Trial1 (patient recruitment 1993–1995 from Canada, France, the Netherlands, and the United States) and the Endoscopic Shunt Insertion Trial5 (patient recruitment 1996–1999 from Canada, the Netherlands, the United Kingdom, and the United States). Permission to use data from these trials was granted by each trial’s principal investigators. All data were rendered anonymous, and data collection adhered to local research ethics protocols. Definitions
Cause of hydrocephalus was categorized as 1 of the following: aqueductal stenosis, brain tumor (all types, including midbrain tumors), CSF infection, head injury, intraventricular hemorrhage (associated with prematurity or other spontaneous causes), myelomeningocele, and other/unknown. The other/unknown category included encephalocele, posterior fossa cyst (for example, DandyWalker and variants), other intracranial cyst (for example, arachnoid cyst and porencephalic cyst), communicating congenital hydrocephalus, other congenital (for example, schizencephaly and holoprosencephaly), and craniosynostosis. Shunt failure was defined as the need for any subsequent surgical procedure for definitive CSF diversion (for shunt malfunction or infection) or death associated with hydrocephalus management.
Statistical Analysis
We performed survival analyses by using Cox proportional hazards models for time to first shunt failure. The primary analysis was a multivariate Cox model that included treatment cohorts (HCRN vs historical), in which we adjusted for patient age at first shunt surgery (< 1 month, 1 to < 6 months, 6 to < 12 months, 1 to < 10
J Neurosurg: Pediatrics / Volume 12 / October 2013
years, and ≥ 10 years) and hydrocephalus etiology (excluding other/unknown). Because the factor of patient age at the time of shunt surgery did not meet the proportional hazards assumption, age adjustment in the reported Cox analysis was performed via stratification. Survival curves were calculated by using the Kaplan-Meier method. All analyses were performed by using SAS statistical software (SAS Institute).
Results
The characteristics of the 1184 HCRN cohort patients and the 720 historical cohort patients are listed in Table 1. Differences between the cohorts were found for patient age and hydrocephalus etiology. Compared with patients in the historical cohort, among patients in the HCRN cohort, mean age was higher at the time of shunt (2.51 vs 1.60 years, p < 0.0001); the proportion of brain tumors was higher and the proportion of myelomeningoceles was lower (p < 0.0001, chi-square test). For survival analyses, the 473 patients (24.8% of the sample) for whom etiology of hydrocephalus was other/ unknown were excluded because of the great heterogeneity of underlying conditions within this group. The survival curves for time to first shunt failure in each cohort are shown in Fig. 1. Separate survival curves for patients with hydrocephalus of the most common etiologies (intraventricular hemorrhage, myelomeningocele, aqueductal stenosis, and brain tumor) are shown in Fig. 2. Aside from patients with brain tumors, a survival advantage was found for patients in the HCRN cohort. The results of the Cox proportional hazards model are shown in Table 2 and confirmed an overall survival advantage for patients TABLE 1: Characteristics of patients with hydrocephalus Characteristic
HCRN Cohort Historical Cohort
no. of patients 1184 period when patients were treated 2008–2012 countries in which patients were Canada, US treated age at treatment, no. (%)
Outcomes of CSF shunting in children: comparison of Hydrocephalus Clinical Research Network cohort with historical controls Clinical article Abhaya V. Kulkarni, M.D., Ph.D.,1 Jay Riva-Cambrin, M.D., M.Sc., 2 Jerry Butler, M.S., 2 Samuel R. Browd, M.D., Ph.D., 3 James M. Drake, M.B.B.Ch., M.Sc.,1 Richard Holubkov, Ph.D., 2 John R. W. Kestle, M.D., M.Sc., 2 David D. Limbrick, M.D., Ph.D., 4 Tamara D. Simon, M.D., M.S.P.H., 3 Mandeep S. Tamber, M.D., Ph.D., 5 John C. Wellons III, M.D., M.S.P.H., 6 and William E. Whitehead, M.D., M.P.H.,7 for the Hydrocephalus Clinical Research Network Hospital for Sick Children, University of Toronto, Ontario, Canada; 2Primary Children’s Medical Center, Salt Lake City, Utah; 3Seattle Children’s Hospital, University of Washington, Seattle, Washington; 4St. Louis Children’s Hospital, St. Louis, Missouri; 5Children’s Hospital of Pittsburgh, Pennsylvania; 6Vanderbilt University, Nashville, Tennessee; and 7Texas Children’s Hospital, Houston, Texas 1
Object. The Hydrocephalus Clinical Research Network (HCRN), which comprises 7 pediatric neurosurgical centers in North America, provides a unique multicenter assessment of the current outcomes of CSF shunting in nonselected patients. The authors present the initial results for this cohort and compare them with results from prospective multicenter trials performed in the 1990s. Methods. Analysis was restricted to patients with newly diagnosed hydrocephalus undergoing shunting for the first time. Detailed perioperative data from 2008 through 2012 for all HCRN centers were prospectively collected and centrally stored by trained research coordinators. Historical control data were obtained from the Shunt Design Trial (1993–1995) and the Endoscopic Shunt Insertion Trial (1996–1999). The primary outcome was time to first shunt failure, which was determined by using Cox regression survival analysis. Results. Mean age of the 1184 patients in the HCRN cohort was older than mean age of the 720 patients in the historical cohort (2.51 years vs 1.60 years, p < 0.0001). The distribution of etiologies differed (p < 0.0001, chi-square test); more tumors and fewer myelomeningoceles caused the hydrocephalus in the HCRN cohort patients. The hazard ratio for first shunt failure significantly favored the HCRN cohort, even after the model was adjusted for the prognostic effects of age and etiology (adjusted HR 0.82, 95% CI 0.69–0.96). Conclusions. Current outcomes of shunting in general pediatric neurosurgery practice have improved over those from the 1990s, although the reasons remain unclear. (http://thejns.org/doi/abs/10.3171/2013.7.PEDS12637)
Key Words • historical cohort • hydrocephalus • pediatric • shunt
A
CSF shunting has been the most widely used treatment for hydrocephalus over the past half century, it is unclear whether outcomes of shunting have improved dramatically over time. Since 2006, the HCRN, a multicenter network of pediatric neurosurgical institutions, has been dedicated to collecting high-quality data on the outcomes of hydrocephalus lthough
Abbreviation used in this paper: HCRN = Hydrocephalus Clinical Research Network.
334
treatment in children.6,11,13 The HCRN currently comprises 7 centers in North America and provides a unique opportunity for assessing the current outcomes of CSF shunting in nonselected patients. The objective of this study was to present the initial results for these patients (HCRN cohort) and compare them with historical data from prospective multicenter trials performed in the This article contains some figures that are displayed in color online but in black-and-white in the print edition.
J Neurosurg: Pediatrics / Volume 12 / October 2013
Outcomes of CSF shunting 1990s (historical cohort).1,3,5 The primary aim was to determine whether the outcomes of CSF shunt failures among children have changed over the past decade.
Methods Population
All patients were 19 years of age or younger; had newly diagnosed, previously untreated hydrocephalus; and were treated by pediatric neurosurgeons at specialized centers. Patients in the HCRN cohort were treated at 1 of 7 network centers (Children’s Hospital of Alabama, Birmingham, AL; Primary Children’s Hospital, Salt Lake City, UT; Seattle Children’s Hospital, Seattle, WA; Children’s Hospital of Pittsburgh, PA; St. Louis Children’s Hospital, St. Louis, MO; Texas Children’s Hospital, Houston, TX; Sick Kids Hospital (Hospital for Sick Children), Toronto, Canada). As part of the HCRN ongoing core data project, which began in April 2008, trained, dedicated research coordinators at each center collect data for all patients undergoing hydrocephalus-related surgery. Data are stored centrally and securely at the Data Coordinating Center in Salt Lake City. To ensure data accuracy and timeliness, standardized audits of data accuracy are performed regularly. Patients in the historical cohort had participated in 1 of 2 prospective trials: the Shunt Design Trial1 (patient recruitment 1993–1995 from Canada, France, the Netherlands, and the United States) and the Endoscopic Shunt Insertion Trial5 (patient recruitment 1996–1999 from Canada, the Netherlands, the United Kingdom, and the United States). Permission to use data from these trials was granted by each trial’s principal investigators. All data were rendered anonymous, and data collection adhered to local research ethics protocols. Definitions
Cause of hydrocephalus was categorized as 1 of the following: aqueductal stenosis, brain tumor (all types, including midbrain tumors), CSF infection, head injury, intraventricular hemorrhage (associated with prematurity or other spontaneous causes), myelomeningocele, and other/unknown. The other/unknown category included encephalocele, posterior fossa cyst (for example, DandyWalker and variants), other intracranial cyst (for example, arachnoid cyst and porencephalic cyst), communicating congenital hydrocephalus, other congenital (for example, schizencephaly and holoprosencephaly), and craniosynostosis. Shunt failure was defined as the need for any subsequent surgical procedure for definitive CSF diversion (for shunt malfunction or infection) or death associated with hydrocephalus management.
Statistical Analysis
We performed survival analyses by using Cox proportional hazards models for time to first shunt failure. The primary analysis was a multivariate Cox model that included treatment cohorts (HCRN vs historical), in which we adjusted for patient age at first shunt surgery (< 1 month, 1 to < 6 months, 6 to < 12 months, 1 to < 10
J Neurosurg: Pediatrics / Volume 12 / October 2013
years, and ≥ 10 years) and hydrocephalus etiology (excluding other/unknown). Because the factor of patient age at the time of shunt surgery did not meet the proportional hazards assumption, age adjustment in the reported Cox analysis was performed via stratification. Survival curves were calculated by using the Kaplan-Meier method. All analyses were performed by using SAS statistical software (SAS Institute).
Results
The characteristics of the 1184 HCRN cohort patients and the 720 historical cohort patients are listed in Table 1. Differences between the cohorts were found for patient age and hydrocephalus etiology. Compared with patients in the historical cohort, among patients in the HCRN cohort, mean age was higher at the time of shunt (2.51 vs 1.60 years, p < 0.0001); the proportion of brain tumors was higher and the proportion of myelomeningoceles was lower (p < 0.0001, chi-square test). For survival analyses, the 473 patients (24.8% of the sample) for whom etiology of hydrocephalus was other/ unknown were excluded because of the great heterogeneity of underlying conditions within this group. The survival curves for time to first shunt failure in each cohort are shown in Fig. 1. Separate survival curves for patients with hydrocephalus of the most common etiologies (intraventricular hemorrhage, myelomeningocele, aqueductal stenosis, and brain tumor) are shown in Fig. 2. Aside from patients with brain tumors, a survival advantage was found for patients in the HCRN cohort. The results of the Cox proportional hazards model are shown in Table 2 and confirmed an overall survival advantage for patients TABLE 1: Characteristics of patients with hydrocephalus Characteristic
HCRN Cohort Historical Cohort
no. of patients 1184 period when patients were treated 2008–2012 countries in which patients were Canada, US treated age at treatment, no. (%)
