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Jonathan Pindrik, Jay Riva-Cambrin, Abhaya V. Kulkarni, Jessica S. Alvey, Ron W. Reeder, Ian F. Pollack, John C. Wellons III, Eric M. Jackson, Curtis J. Rozzelle, William E. Whitehead, David D. Limbrick Jr., Robert P. Naftel, Chevis Shannon, Patrick J. McDonald, Mandeep S. Tamber, Todd C. Hankinson, Jason S. Hauptman, Tamara D. Simon, Mark D. Krieger, Richard Holubkov, John R. W. Kestle and for the Hydrocephalus Clinical Research Network

OBJECTIVE

Few studies have addressed surgical resource utilization—surgical revisions and associated hospital admission days—following shunt insertion or endoscopic third ventriculostomy (ETV) with or without choroid plexus cauterization (CPC) for CSF diversion in hydrocephalus. Study members of the Hydrocephalus Clinical Research Network (HCRN) investigated differences in surgical resource utilization between CSF diversion strategies in hydrocephalus in infants.

METHODS

Patients up to corrected age 24 months undergoing initial definitive treatment of hydrocephalus were reviewed from the prospectively maintained HCRN Core Data Project (Hydrocephalus Registry). Postoperative courses (at 1, 3, and 5 years) were studied for hydrocephalus-related surgeries (primary outcome) and hospital admission days related to surgical revision (secondary outcome). Data were summarized using descriptive statistics and compared using negative binomial regression, controlling for age, hydrocephalus etiology, and HCRN center. The study population was organized into 3 groups (ETV alone, ETV with CPC, and CSF shunt insertion) during the 1st postoperative year and 2 groups (ETV alone and CSF shunt insertion) during subsequent years due to limited long-term follow-up data.

RESULTS

Among 1090 patients, the majority underwent CSF shunt insertion (CSF shunt, 83.5%; ETV with CPC, 10.0%; and ETV alone, 6.5%). Patients undergoing ETV with CPC had a higher mean number of revision surgeries (1.2 ± 1.6) than those undergoing ETV alone (0.6 ± 0.8) or CSF shunt insertion (0.7 ± 1.3) over the 1st year after surgery (p = 0.005). At long-term follow-up, patients undergoing ETV alone experienced a nonsignificant lower mean number of revision surgeries (0.7 ± 0.9 at 3 years and 0.8 ± 1.3 at 5 years) than those undergoing CSF shunt insertion (1.1 ± 1.9 at 3 years and 1.4 ± 2.6 at 5 years) and exhibited a lower mean number of hospital admission days related to revision surgery (3.8 ± 10.3 vs 9.9 ± 27.0, p = 0.042).

CONCLUSIONS

Among initial treatment strategies for hydrocephalus, ETV with CPC yielded a higher surgical revision rate within 1 year after surgery. Patients undergoing ETV alone exhibited a nonsignificant lower mean number of surgical revisions than CSF shunt insertion at 3 and 5 years postoperatively. Additionally, the ETV-alone cohort demonstrated significantly fewer hospital admission days related to surgical management of hydrocephalus within 3 years after surgery. These findings suggest a time-dependent benefit of ETV over CSF shunt insertion regarding surgical resource utilization.

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Brandon A. Sherrod, Rajiv R. Iyer and John R. W. Kestle

OBJECTIVE

Surgical options for managing hydrocephalus secondary to CNS tumors have traditionally included ventriculoperitoneal shunting (VPS) when tumor resection or medical management alone are ineffective. Endoscopic third ventriculostomy (ETV) has emerged as an attractive treatment strategy for tumor-associated hydrocephalus because it offers a lower risk of infection and hardware-related complications; however, relatively little has been written on the topic of ETV specifically for the treatment of tumor-associated hydrocephalus. Here, the authors reviewed the existing literature on the use of ETV in the treatment of tumor-associated hydrocephalus, focusing on the frequency of ETV use and the failure rates in patients with hydrocephalus secondary to CNS tumor.

METHODS

The authors queried PubMed for the following terms: “endoscopic third ventriculostomy,” “tumor,” and “pediatric.” Papers with only adult populations, case reports, and papers published before the year 2000 were excluded. The authors analyzed the etiology of hydrocephalus and failure rates after ETV, and they compared failure rates of ETV with those of VPS where reported.

RESULTS

Thirty-two studies with data on pediatric patients undergoing ETV for tumor-related hydrocephalus were analyzed. Tumors, particularly in the posterior fossa, were reported as the etiology of hydrocephalus in 38.6% of all ETVs performed (984 of 2547 ETVs, range 29%–55%). The ETV failure rate in tumor-related hydrocephalus ranged from 6% to 38.6%, and in the largest studies analyzed (> 100 patients), the ETV failure rate ranged from 10% to 38.6%. The pooled ETV failure rate was 18.3% (199 failures after 1087 procedures). The mean or median follow-up for ETV failure assessment ranged from 6 months to 8 years in these studies. Only 5 studies directly compared ETV with VPS for tumor-associated hydrocephalus, and they reported mixed results in regard to failure rate and time to failure. Overall failure rates appear similar for ETV and VPS over time, and the risk of infection appears to be lower in those patients undergoing ETV. The literature is mixed regarding the need for routine ETV before resection for posterior fossa tumors with associated hydrocephalus.

CONCLUSIONS

Treatment of tumor-related hydrocephalus with ETV is common and is warranted in select pediatric patient populations. Failure rates are overall similar to those of VPS for tumor-associated hydrocephalus.

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Joyce Koueik, Carolina Sandoval-Garcia, John R. W. Kestle, Brandon G. Rocque, David M. Frim, Gerald A. Grant, Robert F. Keating, Carrie R. Muh, W. Jerry Oakes, Ian F. Pollack, Nathan R. Selden, R. Shane Tubbs, Gerald F. Tuite, Benjamin Warf, Victoria Rajamanickam, Aimee Teo Broman, Victor Haughton, Susan Rebsamen, Timothy M. George and Bermans J. Iskandar

OBJECTIVE

Despite significant advances in diagnostic and surgical techniques, the surgical management of Chiari malformation type I (CM-I) with associated syringomyelia remains controversial, and the type of surgery performed is surgeon dependent. This study’s goal was to determine the feasibility of a prospective, multicenter, cohort study for CM-I/syringomyelia patients and to provide pilot data that compare posterior fossa decompression and duraplasty (PFDD) with and without tonsillar reduction.

METHODS

Participating centers prospectively enrolled children suffering from both CM-I and syringomyelia who were scheduled to undergo surgical decompression. Clinical data were entered into a database preoperatively and at 1–2 weeks, 3–6 months, and 1 year postoperatively. MR images were evaluated by 3 independent, blinded teams of neurosurgeons and neuroradiologists. The primary endpoint was improvement or resolution of the syrinx.

RESULTS

Eight clinical sites were chosen based on the results of a published questionnaire intended to remove geographic and surgeon bias. Data from 68 patients were analyzed after exclusions, and complete clinical and imaging records were obtained for 55 and 58 individuals, respectively. There was strong agreement among the 3 radiology teams, and there was no difference in patient demographics among sites, surgeons, or surgery types. Tonsillar reduction was not associated with > 50% syrinx improvement (RR = 1.22, p = 0.39) or any syrinx improvement (RR = 1.00, p = 0.99). There were no surgical complications.

CONCLUSIONS

This study demonstrated the feasibility of a prospective, multicenter surgical trial in CM-I/syringomyelia and provides pilot data indicating no discernible difference in 1-year outcomes between PFDD with and without tonsillar reduction, with power calculations for larger future studies. In addition, the study revealed important technical factors to consider when setting up future trials. The long-term sequelae of tonsillar reduction have not been addressed and would be an important consideration in future investigations.

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Jay Riva-Cambrin, John R. W. Kestle, Curtis J. Rozzelle, Robert P. Naftel, Jessica S. Alvey, Ron W. Reeder, Richard Holubkov, Samuel R. Browd, D. Douglas Cochrane, David D. Limbrick Jr., Chevis N. Shannon, Tamara D. Simon, Mandeep S. Tamber, John C. Wellons III, William E. Whitehead, Abhaya V. Kulkarni and for the Hydrocephalus Clinical Research Network

OBJECTIVE

Endoscopic third ventriculostomy combined with choroid plexus cauterization (ETV+CPC) has been adopted by many pediatric neurosurgeons as an alternative to placing shunts in infants with hydrocephalus. However, reported success rates have been highly variable, which may be secondary to patient selection, operative technique, and/or surgeon training. The objective of this prospective multicenter cohort study was to identify independent patient selection, operative technique, or surgical training predictors of ETV+CPC success in infants.

METHODS

This was a prospective cohort study nested within the Hydrocephalus Clinical Research Network’s (HCRN) Core Data Project (registry). All infants under the age of 2 years who underwent a first ETV+CPC between June 2006 and March 2015 from 8 HCRN centers were included. Each patient had a minimum of 6 months of follow-up unless censored by an ETV+CPC failure. Patient and operative risk factors of failure were examined, as well as formal ETV+CPC training, which was defined as traveling to and working with the experienced surgeons at CURE Children’s Hospital of Uganda. ETV+CPC failure was defined as the need for repeat ETV, shunting, or death.

RESULTS

The study contained 191 patients with a primary ETV+CPC conducted by 17 pediatric neurosurgeons within the HCRN. Infants under 6 months corrected age at the time of ETV+CPC represented 79% of the cohort. Myelomeningocele (26%), intraventricular hemorrhage associated with prematurity (24%), and aqueductal stenosis (17%) were the most common etiologies. A total of 115 (60%) of the ETV+CPCs were conducted by surgeons after formal training. Overall, ETV+CPC was successful in 48%, 46%, and 45% of infants at 6 months, 1 year, and 18 months, respectively. Young age (< 1 month) (adjusted hazard ratio [aHR] 1.9, 95% CI 1.0–3.6) and an etiology of post–intraventricular hemorrhage secondary to prematurity (aHR 2.0, 95% CI 1.1–3.6) were the only two independent predictors of ETV+CPC failure. Specific subgroups of ages within etiology categories were identified as having higher ETV+CPC success rates. Although training led to more frequent use of the flexible scope (p < 0.001) and higher rates of complete (> 90%) CPC (p < 0.001), training itself was not independently associated (aHR 1.1, 95% CI 0.7–1.8; p = 0.63) with ETV+CPC success.

CONCLUSIONS

This is the largest prospective multicenter North American study to date examining ETV+CPC. Formal ETV+CPC training was not found to be associated with improved procedure outcomes. Specific subgroups of ages within specific hydrocephalus etiologies were identified that may preferentially benefit from ETV+CPC.

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Matthew R. Test, Kathryn B. Whitlock, Marcie Langley, Jay Riva-Cambrin, John R. W. Kestle and Tamara D. Simon

OBJECTIVE

Infection is a common complication of cerebrospinal fluid (CSF) shunts, occurring in 6%–20% of children. Although studies are limited, Staphylococcus aureus is thought to cause more rapid and aggressive infection than coagulase-negative Staphylococcus (CONS) or gram-negative organisms. The authors’ objective was to evaluate the relationship between the causative organisms of CSF shunt infection and the timing of infection.

METHODS

The authors performed a retrospective cohort study of children who underwent CSF shunt placement at a tertiary care children’s hospital over a 9-year period and subsequently developed a CSF shunt infection. The primary predictor variable was the causative organism recovered from CSF culture, characterized as S. aureus, CONS, or gram-negative organisms. The primary outcome was time to infection, defined as the number of days from most recent shunt intervention to the diagnosis of the infection. The association between causative organism and time to infection was visualized using Kaplan-Meier curves, and statistical comparisons were made using nonparametric Kruskal-Wallis tests.

RESULTS

Among 103 children in whom a CSF shunt infection developed, the causative organism was CONS in 57 (55%), S. aureus in 19 (18%), and gram-negative organisms in 9 (9%). The median time to infection did not differ (p = 0.81) for infections caused by CONS (20 days, IQR 11–40), S. aureus (26 days, IQR 12–95), and gram-negative organisms (23 days, IQR 17–34).

CONCLUSIONS

No significant difference in time to infection based on the causative organism was observed among children with a CSF shunt infection.

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Vijay M. Ravindra, Robert J. Bollo, Ilyas M. Eli, Julius Griauzde, Arianna Lanpher, Jennifer Klein, Huirong Zhu, Douglas L. Brockmeyer, John R. W. Kestle, William T. Couldwell, R. Michael Scott and Edward Smith

OBJECTIVE

Large experiences with the treatment of pediatric arteriovenous malformations (AVMs) remain relatively rare, with limited data on presentation, treatment, and long-term functional outcomes. Because of the expected long lifespan of children, caregivers are especially interested in outcome measures that assess quality of life. The authors’ intention was to describe the long-term functional outcomes of pediatric patients who undergo AVM surgery and to identify predictors of sustained neurological deficits.

METHODS

The authors analyzed a 21-year retrospective cohort of pediatric patients with intracranial AVMs treated with microsurgery at two institutions. The primary outcome was a persistent neurological deficit at last follow-up. Secondary outcome measures included modified Rankin Scale (mRS) score and independent living.

RESULTS

Overall, 97 patients (mean age 11.1 ± 4.5 years; 56% female) were treated surgically for intracranial AVMs (mean follow-up 77.5 months). Sixty-four patients (66%) presented with hemorrhage, and 45 patients (46%) had neurological deficits at presentation. Radiologically, 39% of lesions were Spetzler-Martin grade II. Thirty-seven patients (38%) with persistent neurological deficits at last follow-up were compared with those without deficits; there were no differences in patient age, presenting Glasgow Coma Scale score, AVM size, surgical blood loss, or duration of follow-up. Multivariate analysis demonstrated that a focal neurological deficit on presentation, AVM size > 3 cm, and lesions in eloquent cortex were independent predictors of persistent neurological deficits at long-term follow-up. Overall, 92% of the children had an mRS score ≤ 2 on long-term follow-up.

CONCLUSIONS

Pediatric patients with AVMs treated with microsurgical resection have good functional and radiological outcomes. There is a high rate (38%) of persistent neurological deficits, which were independently predicted by preoperative deficits, AVMs > 3 cm, and lesions located in eloquent cortex. This information can be useful in counseling families on the likelihood of long-term neurological deficits after cerebral AVM surgery.

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Tamara D. Simon, Matthew P. Kronman, Kathryn B. Whitlock, Samuel R. Browd, Richard Holubkov, John R. W. Kestle, Abhaya V. Kulkarni, Marcie Langley, David D. Limbrick Jr., Thomas G. Luerssen, W. Jerry Oakes, Jay Riva-Cambrin, Curtis Rozzelle, Chevis N. Shannon, Mandeep Tamber, John C. Wellons III, William E. Whitehead and Nicole Mayer-Hamblett

OBJECTIVE

CSF shunt infection treatment requires both surgical and antibiotic decisions. Using the Hydrocephalus Clinical Research Network (HCRN) Registry and 2004 Infectious Diseases Society of America (IDSA) guidelines that were not proactively distributed to HCRN providers, the authors previously found high adherence to surgical recommendations but poor adherence to intravenous (IV) antibiotic duration recommendations. In general, IV antibiotic duration was longer than recommended. In March 2017, new IDSA guidelines expanded upon the 2004 guidelines by including recommendations for selection of specific antibiotics. The objective of this study was to describe adherence to both 2004 and 2017 IDSA guideline recommendations for CSF shunt infection treatment, and to report reinfection rates associated with adherence to guideline recommendations.

METHODS

The authors investigated a prospective cohort of children younger than 18 years of age who underwent treatment for first CSF shunt infection at one of 7 hospitals from April 2008 to December 2012. CSF shunt infection was diagnosed by recovery of bacteria from CSF culture (CSF-positive infection). Adherence to 2004 and 2017 guideline recommendations was determined. Adherence to antibiotics was further classified as longer or shorter duration than guideline recommendations. Reinfection rates with 95% confidence intervals (CIs) were generated.

RESULTS

There were 133 children with CSF-positive infections addressed by 2004 IDSA guideline recommendations, with 124 at risk for reinfection. Zero reinfections were observed among those whose treatment was fully adherent (0/14, 0% [95% CI 0%–20%]), and 15 reinfections were observed among those whose infection treatment was nonadherent (15/110, 14% [95% CI 8%–21%]). Among the 110 first infections whose infection treatment was nonadherent, 74 first infections were treated for a longer duration than guidelines recommended and 9 developed reinfection (9/74, 12% [95% CI 6%–22%]). There were 145 children with CSF-positive infections addressed by 2017 IDSA guideline recommendations, with 135 at risk for reinfection. No reinfections were observed among children whose treatment was fully adherent (0/3, 0% [95% CI 0%–64%]), and 18 reinfections were observed among those whose infection treatment was nonadherent (18/132, 14% [95% CI 8%–21%]).

CONCLUSIONS

There is no clear evidence that either adherence to IDSA guidelines or duration of treatment longer than recommended is associated with reduction in reinfection rates. Because IDSA guidelines recommend shorter IV antibiotic durations than are typically used, improvement efforts to reduce IV antibiotic use in CSF shunt infection treatment can and should utilize IDSA guidelines.

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Prospective multicenter studies in pediatric hydrocephalus

JNSPG 75th Anniversary Invited Review Article

John R. W. Kestle and Jay Riva-Cambrin

Prospective multicenter clinical research studies in pediatric hydrocephalus are relatively rare. They cover a broad spectrum of hydrocephalus topics, including management of intraventricular hemorrhage in premature infants, shunt techniques and equipment, shunt outcomes, endoscopic treatment of hydrocephalus, and prevention and treatment of infection. The research methodologies include randomized trials, cohort studies, and registry-based studies. This review describes prospective multicenter studies in pediatric hydrocephalus since 1990. Many studies have included all forms of hydrocephalus and used device or procedure failure as the primary outcome. Although such studies have yielded useful findings, they might miss important treatment effects in specific subgroups. As multicenter study networks grow, larger patient numbers will allow studies with more focused entry criteria based on known and evolving prognostic factors. In addition, increased use of patient-centered outcomes such as neurodevelopmental assessment and quality of life should be measured and emphasized in study results. Well-planned multicenter clinical studies can significantly affect the care of children with hydrocephalus and will continue to have an important role in improving care for these children and their families.

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Jian Guan, Michael Karsy, Andrea A. Brock, William T. Couldwell, John R. W. Kestle, Randy L. Jensen, Andrew T. Dailey, Erica F. Bisson and Richard H. Schmidt

OBJECTIVE

Overlapping surgery remains a controversial topic in the medical community. Although numerous studies have examined the safety profile of overlapping operations, there are few data on its financial impact. The authors assessed direct hospital costs associated with neurosurgical operations during periods before and after a more stringent overlapping surgery policy was implemented.

METHODS

The authors retrospectively reviewed the records of nonemergency neurosurgical operations that took place during the periods from June 1, 2014, to October 31, 2014 (pre–policy change), and from June 1, 2016, to October 31, 2016 (post–policy change), by any of the 4 senior neurosurgeons authorized to perform overlapping cases during both periods. Cost data as well as demographic, surgical, and hospitalization-related variables were obtained from an institutional tool, the Value-Driven Outcomes database.

RESULTS

A total of 625 hospitalizations met inclusion criteria for cost analysis; of these, 362 occurred prior to the policy change and 263 occurred after the change. All costs were reported as a proportion of the average total hospitalization cost for the entire cohort. There was no significant difference in mean total hospital costs between the prechange and postchange period (0.994 ± 1.237 vs 1.009 ± 0.994, p = 0.873). On multivariate linear regression analysis, neither the policy change (p = 0.582) nor the use of overlapping surgery (p = 0.273) was significantly associated with higher total hospital costs.

CONCLUSIONS

A more restrictive overlapping surgery policy was not associated with a reduction in the direct costs of hospitalization for neurosurgical procedures.