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Brandon G. Rocque, Bonita S. Agee, Eric M. Thompson, Mark Piedra, Lissa C. Baird, Nathan R. Selden, Stephanie Greene, Christopher P. Deibert, Todd C. Hankinson, Sean M. Lew, Bermans J. Iskandar, Taryn M. Bragg, David Frim, Gerald Grant, Nalin Gupta, Kurtis I. Auguste, Dimitrios C. Nikas, Michael Vassilyadi, Carrie R. Muh, Nicholas M. Wetjen, and Sandi K. Lam

OBJECTIVE

In children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty.

METHODS

The authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty.

RESULTS

A total of 359 patients met the inclusion criteria. The patients’ mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17–4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03–5.79), and ventilator dependence (OR 8.45, 95% CI 1.10–65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection.

Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98–0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts.

CONCLUSIONS

This is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.

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Nathan R. Selden

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David C. Sheridan, Craig D. Newgard, Nathan R. Selden, Mubeen A. Jafri, and Matthew L. Hansen

OBJECTIVE

The current gold-standard imaging modality for pediatric traumatic brain injury (TBI) is CT, but it confers risks associated with ionizing radiation. QuickBrain MRI (qbMRI) is a rapid brain MRI protocol that has been studied in the setting of hydrocephalus, but its ability to detect traumatic injuries is unknown.

METHODS

The authors performed a retrospective cohort study of pediatric patients with TBI who were undergoing evaluation at a single Level I trauma center between February 2010 and December 2013. Patients who underwent CT imaging of the head and qbMRI during their acute hospitalization were included. Images were reviewed independently by 2 neuroradiology fellows blinded to patient identifiers. Image review consisted of identifying traumatic mass lesions and their intracranial compartment and the presence or absence of midline shift. CT imaging was used as the reference against which qbMRI was measured.

RESULTS

A total of 54 patients met the inclusion criteria; the median patient age was 3.24 years, 65% were male, and 74% were noted to have a Glasgow Coma Scale score of 14 or greater. The sensitivity and specificity of qbMRI to detect any lesion were 85% (95% CI 73%–93%) and 100% (95% CI 61%–100%), respectively; the sensitivity increased to 100% (95% CI 89%–100%) for clinically important TBIs as previously defined. The mean interval between CT and qbMRI was 27.5 hours, and approximately half of the images were obtained within 12 hours.

CONCLUSIONS

In this retrospective pilot study, qbMRI demonstrated reasonable sensitivity and specificity for detecting a lesion or injury seen with neuroimaging (radiographic TBI) and clinically important acute pediatric TBI.

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Garrett M. Pool, Ryne A. Didier, Dianna Bardo, Nathan R. Selden, and Anna A. Kuang

OBJECTIVE

The aim of this study was to develop soft-tissue and bony anthropometric orbital measurements in a normal pediatric population based upon CT scans.

METHODS

This was a retrospective stratified study of children with ages ranging from birth to 36 months. Head CT images for 204 children were available and obtained with 0.625–1-mm slice widths. Soft-tissue and bone windows were reviewed. Images were oriented in the Frankfort horizontal plane, and the intercanthal (IC), bony interorbital (IO), and bony lateral orbital (LO) distances were measured. Age group stratifications were 0–3, > 3–6, > 6–9, > 9–12, > 12–18, > 18–24, > 24–30, and > 30–36 months. Patients with known syndromes or craniofacial abnormalities were excluded. Statistical analysis included the mean, SD, SEM, 95% CI, and an evaluation of IO:LO ratio.

RESULTS

There was an average of 25.5 patients in each age group (range 25–27 patients). All soft-tissue and bony measurements consistently showed rapid increase from 0–6 months of age, which tapered after age > 12 months. The mean IC, bony IO, and bony LO distances started at 22.22 ± 1.13 mm, 14.16 ± 0.74 mm, and 65.56 ± 1.76 mm, and at 12 months were 27.74 ± 1.01 mm, 16.21 ± 0.75 mm, and 77.98 ± 1.57 mm, respectively. The bony LO position was equivalent to the lateral canthal position and measurements. The IC distance was approximately one-third the lateral canthal distance for all age groups.

CONCLUSIONS

This study established and reported normal anthropometric orbital measurements in a pediatric population using fine-cut craniofacial CT. These measurements are essential when evaluating children with craniofacial anomalies.

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Esther L. Yue, Garth D. Meckler, Ross J. Fleischman, Nathan R. Selden, Dianna M. E. Bardo, Amity K. Chu O'Connor, Eugene T. Vu, Rongwei Fu, and David M. Spiro

OBJECT

Quick brain magnetic resonance imaging (QB-MRI) is a rapid, radiation-free technique to detect life-threatening CSF shunt malfunction. QB-MRI has not been widely studied or adopted. The primary objective of this study was to evaluate the test characteristics of QB-MRI for detecting shunt malfunction. Test characteristics of brain computed tomography (CT) and QB-MRI were then compared. Secondary objectives included comparison of time to study completion and use of sedatives for both modalities, as well as comparison of time to study completion for QB-MRI before and after implementation of a Pediatric Emergency Department (PED) shunt clinical pathway.

METHODS

A retrospective chart review was performed at 2 tertiary care hospital PEDs. The authors reviewed the charts of children who underwent QB-MRI or CT for suspected shunt malfunction between July 2008 and June 2012. They also reviewed the patients' neuroradiology reports and classified ventricular size as positive (enlarged) or negative (normal, smaller, or unchanged). Shunt malfunction was defined by surgical revision within 30 days.

RESULTS

Nine hundred ninety-seven PED visits (involving 724 QB-MRIs and 273 CTs) were included. Surgical revision was performed in 235 cases (23.6%). For QB-MRI, sensitivity was 58.5% (95% CI 51.1%–65.6%) and specificity was 93.3% (90.8%–95.3%). For CT, sensitivity was 53.2% (95% CI 38.1%–67.9%) and specificity was 95.6% (92%–97.9%). The mean time to completion of QB-MRI was 115 minutes versus 83 minutes for CT (difference 32 minutes, 95% CI, 22–42 minutes, p < 0.001). The mean time from presentation to completion of QB-MRI prior to application of the CSF shunt pathway was 132 minutes versus 112 minutes after application of the CSF shunt pathway (difference 20 minutes, 95% CI 5–35 minutes, p = 0.01). Anxiolytic medications were used in 3.7% of CT studies and 4.4% of QB-MRI studies (p = 0.74).

CONCLUSIONS

QB-MRI and CT have similar test characteristics for detecting CSF shunt malfunction in children and similar requirements for sedation. The longer interval from order placement to imaging completion for QB-MRI is arguably justified by reduction of radiation exposure in this population subject to frequent brain imaging.

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Paul Klimo Jr., Garrett T. Venable, Nickalus R. Khan, Douglas R. Taylor, Brandon A. Shepherd, Clinton J. Thompson, and Nathan R. Selden

Object

The application of bibliometric techniques to academic neurosurgery has been the focus of several recent publications. The authors provide here a detailed analysis of all active pediatric neurosurgeons in North America and their respective departments.

Methods

Using Scopus and Google Scholar, a bibliometric profile for every known active pediatric neurosurgeon in North America was created using the following citation metrics: h-, contemporary h-, g-, and e-indices and the m-quotient. Various subgroups were compared. Departmental productivity from 2008 through 2013 was measured, and departments were ranked on the basis of cumulative h- and e-indices and the total number of publications and citations. Lorenz curves were created, and Gini coefficients were calculated for all departments with 4 or more members.

Results

Three hundred twelve pediatric neurosurgeons (260 male, 52 female) were included for analysis. For the entire group, the median h-index, m-quotient, contemporary h-, g-, and e-indices, and the corrected g- and e-indices were 10, 0.59, 7, 18, 17, 1.14, and 1.01, respectively; the range for each index varied widely. Academic pediatric neurosurgeons associated with fellowship programs (compared with unassociated neurosurgeons), academic practitioners (compared with private practitioners), and men (compared with women) had superior measurements. There was no significant difference between American and Canadian pediatric neurosurgeons. The mean Gini coefficient for publications was 0.45 (range 0.18–0.70) and for citations was 0.53 (range 0.25–0.80).

Conclusions

This study represents the most exhaustive evaluation of academic productivity for pediatric neurosurgeons in North America to date. These results should serve as benchmarks for future studies.

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Eric M. Thompson, Lissa C. Baird, and Nathan R. Selden

Object

Growing concern about potential adverse effects of ionizing radiation exposure during imaging studies is particularly relevant to the pediatric population. To decrease radiation exposure, many institutions use rapid-sequence (or quick-brain) MRI to evaluate cerebral ventricle size. There are obstacles, however, to widespread implementation of this imaging modality. The purpose of this study was to define and quantify these obstacles to positively affect institutional and governmental policy.

Methods

A 9-question survey was emailed to pediatric neurosurgeons who were either members or candidate members of the American Society of Pediatric Neurosurgeons at every one of 101 institutions in the US and Canada having such a neurosurgeon on staff. Responses were compiled and descriptive statistics were performed.

Results

Fifty-six institutions completed the survey. Forty-four (79%) of the 56 institutions currently have a rapid-sequence MRI protocol to evaluate ventricle size, while 36 (64%) use it routinely. Of the 44 institutions with a rapid-sequence MRI protocol, 29 (66%) have had a rapid-sequence MRI protocol for less than 5 years while 39 (89%) have had a rapid-sequence MRI protocol for no more than 10 years. Thirty-six (88%) of 41 rapid-sequence MRI users responding to this question obtain a T2-weighted rapid-sequence MRI while 13 (32%) obtain a T1-weighted rapid-sequence MRI. Twenty-eight (64%) of 44 institutions never use sedation while an additional 12 (27%) rarely use sedation to obtain a rapid-sequence MRI (less than 5% of studies). Of the institutions with an established rapid-sequence MRI protocol, obstacles to routine use include lack of emergency access to MRI facilities in 18 (41%), lack of staffing of MRI facilities in 12 (27%), and the inability to reimburse a rapid-sequence MRI protocol in 6 (14%). In the 12 institutions without rapid-sequence MRI, obstacles to implementation include lack of emergency access to MRI facilities in 8 (67%), lack of staffing of MRI facilities in 7 (58%), the inability to reimburse in 3 (25%), and lack of administrative support in 3 (25%). To evaluate pediatric head trauma, 53 (96%) of 55 institutions responding to this question use noncontrast CT, no institution uses rapid-sequence MRI, and only 2 (4%) use standard MRI.

Conclusions

Many North American institutions have a rapid-sequence MRI protocol to evaluate ventricle size, with most developing this technique within the past 5 years. Most institutions never use sedation, and most obtain T2-weighted sequences. The greatest obstacles to the routine use of rapid-sequence MRI in institutions with and in those without a rapid-sequence MRI protocol are the lack of emergency access and staffing of the MRI facility during nights and weekends.

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Eric M. Thompson, Michael J. Strong, Garth Warren, Randy L. Woltjer, and Nathan R. Selden

Object

The pathophysiology of tethered cord syndrome (TCS) is uncertain; however, it has been suggested that fibrous and fatty elements within the filum terminale (FT) play a role. The objective of this study was to describe the radiological and histological features of the FT in TCS and determine if there are associations between those features and clinical outcomes, complications, and urodynamics.

Methods

In this retrospective study, histological, MRI, and clinical data obtained in 293 patients with TCS who underwent FT transection were reviewed and analyzed in a multivariate analysis.

Results

The median patient age was 4.9 years (range 0.3–64.3 years). On MRI, a fatty filum was present in 65% of patients and a thickened filum (> 2 mm) was seen in 45%. Histologically, the FT contained prominent fibrous tissue in 95%, nerve twigs in 79%, adipose tissue in 59%, and vascular tissue in 36%. Histological features associated with a thickened filum on MR images were adipose tissue (OR 3.5, p < 0.001), nerve twigs (OR 2.2, p = 0.028), and vascular tissue (OR 0.5, p = 0.025). Adipose tissue was associated with a conus level below the L2–3 disc space (OR 2.3, p = 0.031) and with a fatty filum on imaging (OR 9.8, p < 0.001). Nerve twigs were associated with abnormal urodynamics (OR 10.9, p = 0.049). The only variable predictive of clinical improvement was conus level; patients with conus levels caudal to L-2 were less likely to improve postoperatively (OR 0.3, p = 0.042).

Conclusions

Fibrous tissue was ubiquitous and may be important in the pathophysiology of TCS. Nerve twigs and adipose tissue were associated with abnormal urodynamics and low-lying coni, respectively. Although the majority of patients clinically improved, patients with normal conus levels had significantly better outcomes.

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Nathan R. Selden, Amira Al-Uzri, Stephen L. Huhn, Thomas K. Koch, Darryn M. Sikora, Mina D. Nguyen-Driver, Daniel J. Guillaume, Jeffrey L. Koh, Sakir H. Gultekin, James C. Anderson, Hannes Vogel, Trenna L. Sutcliffe, Yakop Jacobs, and Robert D. Steiner

Object

Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model.

Methods

HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression.

Results

Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immunosuppression. The surgery, immunosuppression, and cell transplantation were well tolerated. Adverse events following transplantation were consistent with the underlying disease, and none were directly attributed to the donor cells. Observations regarding efficacy of the intervention were limited by the enrollment criteria requiring that patients be in advanced stages of disease.

Conclusions

This study represents the first-in-human clinical trial involving transplantation of a purified population of human neural stem cells for a neurodegenerative disorder. The feasibility of this approach and absence of transplantation-related serious adverse events support further exploration of HuCNS-SC transplantation as a potential treatment for select subtypes of NCL, and possibly for other neurodegenerative disorders. Clinical trial registration no.: NCT00337636 (ClinicalTrials.gov).