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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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John R. W. Kestle, Amy Lee, Richard C. E. Anderson, Barbu Gociman, Kamlesh B. Patel, Matthew D. Smyth, Craig Birgfeld, Ian F. Pollack, Jesse A. Goldstein, Mandeep Tamber, Thomas Imahiyerobo, Faizi A. Siddiqi and for the Synostosis Research Group

OBJECTIVE

The authors created a collaborative network, the Synostosis Research Group (SynRG), to facilitate multicenter clinical research on craniosynostosis. To identify common and differing practice patterns within the network, they assessed the SynRG surgeons’ management preferences for sagittal synostosis. These results will be incorporated into planning cooperative studies.

METHODS

The SynRG consists of 12 surgeons at 5 clinical sites. An email survey was distributed to SynRG surgeons in late 2016, and responses were collected through early 2017. Responses were collated and analyzed descriptively.

RESULTS

All of the surgeons—7 plastic/craniofacial surgeons and 5 neurosurgeons—completed the survey. They varied in both experience (1–24 years) and sagittal synostosis case volume in the preceding year (5–45 cases). Three sites routinely perform preoperative CT scans. The preferred surgical technique for children younger than 3 months is strip craniectomy (10/12 surgeons), whereas children older than 6 months are all treated with open cranial vault surgery. Pre-incision cefazolin, preoperative complete blood count panels, and an arterial line were used by most surgeons, but tranexamic acid was used routinely at 3 sites and never at the other 2 sites. Among surgeons performing endoscopic strip craniectomy surgery (SCS), most create a 5-cm-wide craniectomy, whereas 2 surgeons create a 2-cm strip. Four surgeons routinely send endoscopic SCS patients to the intensive care unit after surgery. Two of the 5 sites routinely obtain a CT scan within the 1st year after surgery.

CONCLUSIONS

The SynRG surgeons vary substantially in the use of imaging, the choice of surgical procedure and technique, and follow-up. A collaborative network will provide the opportunity to study different practice patterns, reduce variation, and contribute multicenter data on the management of children with craniosynostosis.

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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.

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Michael Karsy, Fraser Henderson Jr., Steven Tenny, Jian Guan, Jeremy W. Amps, Allan H. Friedman, Alejandro M. Spiotta, Sunil Patel, John R. W. Kestle, Randy L. Jensen and William T. Couldwell

OBJECTIVE

The analysis of resident research productivity in neurosurgery has gained significant recent interest. Resident scholarly output affects departmental productivity, recruitment of future residents, and likelihood of future research careers. To maintain and improve opportunities for resident research, the authors evaluated factors that affect resident attitudes toward neurosurgical research on a national level.

METHODS

An online survey was distributed to all US neurosurgical residents. Questions assessed interest in research, perceived departmental support of research, and resident-perceived limitations in pursuing research. Residents were stratified based on number of publications above the median (AM; ≥ 14) or below the median (BM; < 14) for evaluation of factors influencing productivity.

RESULTS

A total of 278 resident responses from 82 US residency programs in 30 states were included (a 20% overall response rate). Residents predominantly desired future academic positions (53.2%), followed by private practice with some research (40.3%). Residents reported a mean ± SD of 11 ± 14 publications, which increased with postgraduate year level. The most common type of research involved retrospective cohort studies (24%) followed by laboratory/benchtop (19%) and case reports (18%). Residents as a group spent on average 14.1 ± 18.5 hours (median 7.0 hours) a week on research. Most residents (53.6%) had ≥ 12 months of protected research time. Mentorship (92.4%), research exposure (89.9%), and early interest in science (78.4%) had the greatest impact on interest in research while the most limiting factors were time (91.0%), call scheduling (47.1%), and funding/grants (37.1%). AM residents cited research exposure (p = 0.003), neurosurgery conference exposure (p = 0.02), formal research training prior to residency (p = 0.03), internal funding sources (p = 0.05), and software support (p = 0.02) as most important for their productivity. Moreover, more productive residents applied and received a higher number of < $10,000 and ≥ $10,000 grants (p < 0.05). A majority of residents (82.4%) agreed or strongly agreed with pursuing research throughout their professional careers. Overall, about half of residents (49.6%) were encouraged toward continued neurosurgical research, while the rest were neutral (36.7%) or discouraged (13.7%). Free-text responses helped to identify solutions on a departmental, regional, and national level that could increase interest in neurosurgical research.

CONCLUSIONS

This survey evaluates various factors affecting resident views toward research, which may also be seen in other specialties. Residents remain enthusiastic about neurosurgical research and offer several solutions to the ever-scarce commodities of time and funding within academic medicine.

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

OBJECTIVE

CSF shunt infection requires both surgical and antibiotic treatment. Surgical treatment includes either total shunt removal with external ventricular drain (EVD) placement followed by new shunt insertion, or distal shunt externalization followed by new shunt insertion once the CSF is sterile. Antibiotic treatment includes the administration of intravenous antibiotics. The Hydrocephalus Clinical Research Network (HCRN) registry provides a unique opportunity to understand reinfection following treatment for CSF shunt infection. This study examines the association of surgical and antibiotic decisions in the treatment of first CSF shunt infection with reinfection.

METHODS

A prospective cohort study of children undergoing treatment for first CSF infection at 7 HCRN hospitals from April 2008 to December 2012 was performed. The HCRN consensus definition was used to define CSF shunt infection and reinfection. The key surgical predictor variable was surgical approach to treatment for CSF shunt infection, and the key antibiotic treatment predictor variable was intravenous antibiotic selection and duration. Cox proportional hazards models were constructed to address the time-varying nature of the characteristics associated with shunt surgeries.

RESULTS

Of 233 children in the HCRN registry with an initial CSF shunt infection during the study period, 38 patients (16%) developed reinfection over a median time of 44 days (interquartile range [IQR] 19–437). The majority of initial CSF shunt infections were treated with total shunt removal and EVD placement (175 patients; 75%). The median time between infection surgeries was 15 days (IQR 10–22). For the subset of 172 infections diagnosed by CSF culture, the mean ± SD duration of antibiotic treatment was 18.7 ± 12.8 days. In all Cox proportional hazards models, neither surgical approach to infection treatment nor overall intravenous antibiotic duration was independently associated with reinfection. The only treatment decision independently associated with decreased infection risk was the use of rifampin. While this finding did not achieve statistical significance, in all 5 Cox proportional hazards models both surgical approach (other than total shunt removal at initial CSF shunt infection) and nonventriculoperitoneal shunt location were consistently associated with a higher hazard of reinfection, while the use of ultrasound was consistently associated with a lower hazard of reinfection.

CONCLUSIONS

Neither surgical approach to treatment nor antibiotic duration was associated with reinfection risk. While these findings did not achieve statistical significance, surgical approach other than total removal at initial CSF shunt infection was consistently associated with a higher hazard of reinfection in this study and suggests the feasibility of controlling and standardizing the surgical approach (shunt removal with EVD placement). Considerably more variation and equipoise exists in the duration and selection of intravenous antibiotic treatment. Further consideration should be given to the use of rifampin in the treatment of CSF shunt infection. High-quality studies of the optimal duration of antibiotic treatment are critical to the creation of evidence-based guidelines for CSF shunt infection treatment.

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

OBJECTIVE

High-quality data comparing endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) to shunt and ETV alone in North America are greatly lacking. To address this, the Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study of ETV+CPC in infants. Here, these prospective data are presented and compared to prospectively collected data from a historical cohort of infants treated with shunt or ETV alone.

METHODS

From June 2014 to September 2015, infants (corrected age ≤ 24 months) requiring treatment for hydrocephalus with anatomy suitable for ETV+CPC were entered into a prospective study at 9 HCRN centers. The rate of procedural failure (i.e., the need for repeat hydrocephalus surgery, hydrocephalus-related death, or major postoperative neurological deficit) was determined. These data were compared with a cohort of similar infants who were treated with either a shunt (n = 969) or ETV alone (n = 74) by creating matched pairs on the basis of age and etiology. These data were obtained from the existing prospective HCRN Core Data Project. All patients were observed for at least 6 months.

RESULTS

A total of 118 infants underwent ETV+CPC (median corrected age 1.3 months; common etiologies including myelomeningocele [30.5%], intraventricular hemorrhage of prematurity [22.9%], and aqueductal stenosis [21.2%]). The 6-month success rate was 36%. The most common complications included seizures (5.1%) and CSF leak (3.4%). Important predictors of treatment success in the survival regression model included older age (p = 0.002), smaller preoperative ventricle size (p = 0.009), and greater degree of CPC (p = 0.02). The matching algorithm resulted in 112 matched pairs for ETV+CPC versus shunt alone and 34 matched pairs for ETV+CPC versus ETV alone. ETV+CPC was found to have significantly higher failure rate than shunt placement (p < 0.001). Although ETV+CPC had a similar failure rate compared with ETV alone (p = 0.73), the matched pairs included mostly infants with aqueductal stenosis and miscellaneous other etiologies but very few patients with intraventricular hemorrhage of prematurity.

CONCLUSIONS

Within a large and broad cohort of North American infants, our data show that overall ETV+CPC appears to have a higher failure rate than shunt alone. Although the ETV+CPC results were similar to ETV alone, this comparison was limited by the small sample size and skewed etiological distribution. Within the ETV+CPC group, greater extent of CPC was associated with treatment success, thereby suggesting that there are subgroups who might benefit from the addition of CPC. Further work will focus on identifying these subgroups.