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Shelly Wang, Scellig Stone, Alexander G. Weil, Aria Fallah, Benjamin C. Warf, John Ragheb, Sanjiv Bhatia and Abhaya V. Kulkarni

OBJECTIVE

Endoscopic third ventriculostomy (ETV)/choroid plexus cauterization (CPC) has become an increasingly common technique for the treatment of infant hydrocephalus. Both flexible and rigid neuroendoscopy can be used, with little empirical evidence directly comparing the two. Therefore, the authors used a propensity score–matched cohort and survival analysis to assess the comparative efficacy of flexible and rigid neuroendoscopy.

METHODS

Individual data were collected through retrospective review of infants younger than 2 years of age, treated at 1 of 2 hospitals: 1) Boston Children's Hospital, exclusively utilizing flexible neuroendoscopy, and 2) Nicklaus Children's Hospital-Jackson Memorial Hospital, exclusively utilizing rigid neuroendoscopy. Patient characteristics and postoperative outcomes were assessed. A propensity score model was developed to balance patient characteristics in the case mix.

RESULTS

A propensity score model for neuroendoscope type was developed with 5 independent variables: chronological age, sex, hydrocephalus etiology, prior CSF diversion, and prepontine scarring. Propensity score decile-adjusted and 1-to-1 nearest-neighbor matching analysis revealed that compared with flexible neuroendoscopy, rigid neuroendoscopy had an ETV/CPC failure odds ratio (OR) of 1.43 (p = 0.31) and 1.31 (p = 0.47), respectively, compared with an unadjusted OR of 2.40 (p = 0.034). Furthermore, in a Cox regression analysis controlled by propensity score, rigid neuroendoscopy had a hazard ratio (HR) of 1.10 (p = 0.70), compared with an unadjusted HR of 1.61 (p = 0.031).

CONCLUSIONS

Although unadjusted analysis suggested worse ETV/CPC outcomes for infants treated by rigid neuroendoscopy, much of the difference could be attributed to the case mix and other predictors of outcome. A larger sample observational study or randomized controlled trials are required to provide evidence-based guidelines on ETV/CPC technique.

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John R. W. Kestle, Abhaya V. Kulkarni and Benjamin C. Warf

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Jason G. Mandell, Abhaya V. Kulkarni, Benjamin C. Warf and Steven J. Schiff

OBJECT

The evaluation of hydrocephalus remains focused on ventricular size, yet the goal of treatment is to allow for healthy brain development. It is likely that brain volume is more related to cognitive development than is fluid volume in children with hydrocephalus. This study tests this hypothesis by comparing brain and fluid volumes with neurocognitive outcome in pediatric patients with hydrocephalus.

METHODS

Warf and colleagues previously acquired CT scans for pediatric patients in Uganda with myelomeningocele, measured frontal–occipital horn ratio (FOHR), and administered the modified Bayley Scales of Infant Development, third edition (BSID-III) to measure neurocognitive outcome that did not correlate with FOHR. In this present study, brain and fluid volumes were measured in 33 of these patients, 26 of whom required surgical treatment for hydrocephalus. Linear discrimination analysis (LDA) was used to test whether age-normalized brain and fluid volumes can discriminate neurocognitive outcome.

RESULTS

Hydrocephalic patients show normal to small brain volumes and substantially larger fluid volumes compared with normal values. FOHR correlates highly with fluid volume (r = 0.84, p < 0.001) and substantially less with brain volume (r = −0.37, p = 0.03), while brain and fluid volumes do not correlate with each other (p = 0.99). Brain and CSF volumes correlated best with fine motor (p = 0.03, p = 0.01), cognitive (p = 0.05, p = 0.09), and expressive communication (p = 0.08, p = 0.08) scores. A combination of these 3 scores was used as a multivariate measure of neurocognitive outcome. Brain volume alone, unlike fluid volume, could discriminate high from low cognitive outcome (by t-test and ANOVA). It was shown that a combination of age-normalized brain and fluid volumes can discriminate neurocognitive outcome by 2-way LDA (p < 0.01) and 3-way LDA (p < 0.01). The multivariate LDA demonstrated the contribution of large fluid volume to a decrement in cognition.

CONCLUSIONS

Hydrocephalus is treated by normalizing CSF, but normal brain development depends on brain growth. A combination of brain and CSF volumes appears to be significantly more powerful at predicting good versus poor neurocognitive outcomes in patients with hydrocephalus than either volume alone.

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James Drake

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Benjamin C. Warf, Salman Bhai, Abhaya V. Kulkarni and John Mugamba

Object

It is not known whether previous endoscopic third ventriculostomy (ETV) affects the risk of shunt failure. Different epochs of hydrocephalus treatment at the CURE Children's Hospital of Uganda (CCHU)—initially placing CSF shunts in all patients, then attempting ETV in all patients, and finally attempting ETV combined with choroid plexus cauterization (CPC) in all patients—provided the opportunity to assess whether prior endoscopic surgery affected shunt survival.

Methods

With appropriate institutional approvals, the authors reviewed the CCHU clinical database to identify 2329 patients treated for hydrocephalus from December 2000 to May 2007. Initial ventriculoperitoneal (VP) shunt placement was performed in 900 patients under one of three circumstances: 1) primary nonselective VP shunt placement with no endoscopy (255 patients); 2) VP shunt placement at the time of abandoned ETV attempt (with or without CPC) (370 patients); 3) VP shunt placement subsequent to a completed but failed ETV (with or without CPC) (275 patients). We analyzed time to shunt failure using the Kaplan-Meier method to construct survival curves, Cox proportional hazards regression modeling, and risk-adjusted analyses to account for possible confounding differences among these groups.

Results

Shunt failure occurred in 299 patients, and the mean duration of follow-up for the remaining 601 was 28.7 months (median 18.8, interquartile range 4.1–46.3). There was no significant difference in operative mortality (p = 0.07 by log-rank and p = 0.14 by Cox regression adjusted for age and hydrocephalus etiology) or shunt infection (p = 0.94, log-rank) among the 3 groups. There was no difference in shunt survival between patients treated with primary shunt placement and those who underwent shunt placement at the time of an abandoned ETV attempt (adjusted hazard ratio [HR] 1.14, 95% CI 0.86–1.51, p = 0.35).

Those who underwent shunt placement after a completed but failed ETV (with or without CPC) had a lower risk of shunt failure (p = 0.008, log-rank), with a hazard ratio (adjusted for age at shunting and etiology) of 0.72 (95% CI 0.53–0.98), p = 0.03, compared with those who underwent primary shunt placement without endoscopy; but this was observed only in patients with postinfectious hydrocephalus (PIH) (adjusted HR 0.55, 95% CI 0.36–0.85, p = 0.007), and no effect was apparent for hydrocephalus of noninfectious etiologies (adjusted HR 0.98, 95% CI 0.64–1.50, p = 0.92). Improved shunt survival after failed ETV in the PIH group may be an artifact of selection arising from the inherent heterogeneity of ventricular damage within that group, or a consequence of the timing of shunt placement. The anticipated benefit of CPC in preventing future ventricular catheter obstruction was not observed.

Conclusions

A paradigm for infant hydrocephalus involving intention to treat by ETV with or without CPC had no adverse effect on mortality or on subsequent shunt survival or infection risk. This study failed to demonstrate a positive effect of prior ETV or CPC on shunt survival.

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Benjamin C. Warf, Ernest J. Wright III and Abhaya V. Kulkarni

Object

The survival of infants treated for myelomeningocele (MM) and hydrocephalus in Uganda is unknown. This study investigated 5-year survival and the factors that influenced death in these patients.

Methods

All 140 children from 16 contiguous districts in southeastern Uganda presenting to CURE Children's Hospital of Uganda for repair of MM prior to 6 months of age between December 2000 and December 2004 comprised the study cohort. Nine patients died within 1 month (6.4% operative mortality) and were excluded from further analysis. Sixty-seven (51%) required treatment for hydrocephalus. Survival status could not be determined for 3 patients (2%). Circumstances of death were ascertained by hospital record or interview. The Kaplan-Meier method was used for survival analysis. Association between survival and district of origin, age at MM closure, MM lesion level, presence of hydrocephalus, and method of hydrocephalus treatment were investigated.

Results

The median follow-up was 86 months. Seventy-three children (56%) were alive at the time of the study, and 81 (63%) had survived more than 5 years. The under-5 mortality rate was 37% (2.5 times greater than the general population). Only 4 deaths appeared directly related to hydrocephalus or MM. There was no significant association between survival and age at MM closure, MM lesion level, presence of hydrocephalus, or its method of treatment. Mortality was lower, approaching that for their unaffected peers, in districts with community-based rehabilitation programs (p = 0.001).

Conclusions

Community-based support following surgical interventions for MM and hydrocephalus appears essential to the continued survival of these children in Africa.

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Benjamin C. Warf, John Mugamba and Abhaya V. Kulkarni

Object

In Uganda, childhood hydrocephalus is common and difficult to treat. In some children, endoscopic third ventriculostomy (ETV) can be successful and avoid dependence on a shunt. This can be especially beneficial in Uganda, because of the high risk of infection and long-term failure associated with shunting. Therefore, the authors developed and validated a model to predict the chances of ETV success, taking into account the unique characteristics of a large sub-Saharan African population.

Methods

All children presenting with hydrocephalus at CURE Children's Hospital of Uganda (CCHU) between 2001 and 2007 were offered ETV as first-line treatment and were prospectively followed up. A multivariable logistic regression model was built using ETV success at 6 months as the outcome. The model was derived on 70% of the sample (training set) and validated on the remaining 30% (validation set).

Results

Endoscopic third ventriculostomy was attempted in 1406 patients. Of these, 427 were lost to follow-up prior to 6 months. In the remaining 979 patients, the ETV was aborted in 281 due to poor anatomy/visibility and in 310 the ETV failed during the first 6 months. Therefore, a total of 388 of 979 (39.6% and [55.6% of completed ETVs]) procedures were successful at 6 months. The mean age at ETV was 12.6 months, and 57.8% of cases were postinfectious in origin. The authors' logistic regression model contained the following significant variables: patient age at ETV, cause of hydrocephalus, and whether choroid plexus cauterization was performed. In the training set (676 patients) and validation set (303 patients), the model was able to accurately predict the probability of successful ETV (Hosmer-Lemeshow p value > 0.60 and C statistic > 0.70). The authors developed the simplified CCHU ETV Success Score that can be used in the field to predict the probability of ETV success.

Conclusions

The authors' model will allow clinicians to accurately identify children with a good chance of successful outcome with ETV, taking into account the unique characteristics and circumstances of the Ugandan population.

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Benjamin C. Warf and Abhaya V. Kulkarni

Object

In the setting of a developing country where preoperative imaging may be limited, the authors wished to determine whether cisternal scarring or aqueduct patency at the time of surgery was sufficiently predictive of the failure of endoscopic third ventriculostomy (ETV) to justify shunt placement at the time of the initial operation.

Methods

The status of the prepontine cistern and aqueduct at the time of ventriculoscopy was prospectively recorded in 403 children in whom an ETV had been completed. Kaplan-Meier methods were used to construct survival curves. A Cox proportional hazards model was used to provide estimates of HRs for the time to ETV failure. Several independent variables were tested in a single multivariable model, including those previously shown to be associated with ETV survival, that is, age, hydrocephalus etiology, and extent of choroid plexus cauterization (CPC). In addition, intraoperative variables of particular interest were included in the analysis: status of the aqueduct at surgery (closed vs open) and status of the prepontine cistern at surgery (scarred vs clean/unscarred). Multicollinearity was not a concern since the variance inflation factors for all variables were < 2. The examination of stratified survival curves confirmed the appropriateness of the proportional hazards assumption for each variable.

Results

Overall actuarial 3-year success was 57%. Consistent with previous results, age, hydrocephalus etiology, and extent of CPC were significantly associated with ETV success. A closed aqueduct and an unscarred cistern were each independently associated with significantly better ETV success (HRs of 0.66 and 0.44, respectively). The presence of cisternal scarring more than doubled the risk of ETV failure, and an open aqueduct increased the risk of failure by 50%.

Conclusions

Intraoperative observations of the aqueduct and prepontine cistern are independent predictors of the risk of ETV failure and can be used to further refine outcome predictions based on age, hydrocephalus etiology, and extent of CPC. Further studies will test validity in several African centers and determine what threshold of failure risk should prompt shunt placement at the initial operation.