Search

OBJECTIVE The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

OBJECTIVE The diagnosis of single-suture craniosynostosis can be made by physical examination, but the use of confirmatory imaging is common practice. The authors sought to investigate preoperative imaging use and to describe intracranial findings in children with single-suture synostosis from a large, prospective multicenter cohort. METHODS In this study from the Synostosis Research Group, the study population included children with clinically diagnosed single-suture synostosis between March 1, 2017, and October 31, 2020, at 5 institutions. The primary analysis correlated the clinical diagnosis and imaging diagnosis; secondary outcomes included intracranial findings by pathological suture type. RESULTS A total of 403 children (67% male) were identified with single-suture synostosis. Sagittal (n = 267), metopic (n = 77), coronal (n = 52), and lambdoid (n = 7) synostoses were reported; the most common presentation was abnormal head shape (97%), followed by a palpable or visible ridge (37%). Preoperative cranial imaging was performed in 90% of children; findings on 97% of these imaging studies matched the initial clinical diagnosis. Thirty-one additional fused sutures were identified in 18 children (5%) that differed from the clinical diagnosis. The most commonly used imaging modality by far was CT (n = 360), followed by radiography (n = 9) and MRI (n = 7). Most preoperative imaging was ordered as part of a protocolized pathway (67%); some images were obtained as a result of a nondiagnostic clinical examination (5.2%). Of the 360 patients who had CT imaging, 150 underwent total cranial vault surgery and 210 underwent strip craniectomy. The imaging findings influenced the surgical treatment 0.95% of the time. Among the 24% of children with additional (nonsynostosis) abnormal findings on CT, only 3.5% required further monitoring. CONCLUSIONS The authors found that a clinical diagnosis of single-suture craniosynostosis and the findings on CT were the same with rare exceptions. CT imaging very rarely altered the surgical treatment of children with single-suture synostosis.

OBJECTIVE Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P

OBJECTIVEIn patients with Chiari malformation type I (CM-I) and a syrinx who also have scoliosis, clinical and radiological predictors of curve regression after posterior fossa decompression are not well known. Prior reports indicate that age younger than 10 years and a curve magnitude < 35° are favorable predictors of curve regression following surgery. The aim of this study was to determine baseline radiological factors, including craniocervical junction alignment, that might predict curve stability or improvement after posterior fossa decompression.METHODSA large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and a syrinx (≥ 3 mm in width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°) in patients who underwent posterior fossa decompression and who also had follow-up imaging.RESULTSOf 825 patients with CM-I and a syrinx, 251 (30.4%) were noted to have scoliosis present at the time of diagnosis. Forty-one (16.3%) of these patients underwent posterior fossa decompression and had follow-up imaging to assess for scoliosis. Twenty-three patients (56%) were female, the mean age at time of CM-I decompression was 10.0 years, and the mean follow-up duration was 1.3 years. Nine patients (22%) had stable curves, 16 (39%) showed improvement (> 5°), and 16 (39%) displayed curve progression (> 5°) during the follow-up period. Younger age at the time of decompression was associated with improvement in curve magnitude; for those with curves of ≤ 35°, 17% of patients younger than 10 years of age had curve progression compared with 64% of those 10 years of age or older (p = 0.008). There was no difference by age for those with curves > 35°. Tonsil position, baseline syrinx dimensions, and change in syrinx size were not associated with the change in curve magnitude. There was no difference in progression after surgery in patients who were also treated with a brace compared to those who were not treated with a brace for scoliosis.CONCLUSIONSIn this cohort of patients with CM-I, a syrinx, and scoliosis, younger age at the time of decompression was associated with improvement in curve magnitude following surgery, especially in patients younger than 10 years of age with curves of ≤ 35°. Baseline tonsil position, syrinx dimensions, frontooccipital horn ratio, and craniocervical junction morphology were not associated with changes in curve magnitude after surgery.

OBJECTIVEFactors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established.METHODSUsing the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length.RESULTSThe authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16–0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34–1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12–0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02–2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31–3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67–5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate.CONCLUSIONSThese data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.

Pilocytic astrocytomas are the commonest childhood brain tumor. They are typically benign and usually are solitary neoplasms. To our knowledge, only one report of a pilocytic astrocytoma with leukemia has been previously issued. We herein describe the first case with documented histopathology of a 2-year-old boy who had a cerebellar pilocytic astrocytoma co-localized with an acute B-lymphoblastic leukemia. We speculate that chemotactic migration of leukemic cells to the pilocytic astrocytoma may be partly mediated through vascular endothelial growth factor (VEGF) and VEGF receptors.

Background: Occipitocervical distraction injuries (OCDI) in children occur on a wide spectrum of severity, and decisions about treatment suffer from a lack of rigorous guidelines and significant inter-institutional variability. While clear cases of frank atlanto-occipital dislocation (AOD) are treated with surgical stabilization, the approach for less severe cases of OCDI is not standardized. These patients require a careful assessment of both radiographic and clinical criteria, as part of a complex risk-benefit analysis, to establish whether occipitocervical fusion (OCF) is indicated. Here, we performed a systematic review of the literature that describes traumatic OCDI in children < 18 years of age. Summary: We performed a systematic review, according to PRISMA guidelines, of children < 18 years of age presenting with traumatic etiologies of OCDI. We searched PubMed to identify papers congruent with these criteria. Exclusion criteria included (1) reports on atraumatic causes of OCDI and (2) studies with insufficient clinical and radiographic details on individual patients. We identified 16 reports describing a total of 144 patients treated for pediatric traumatic OCDI. Based on the synthesis of these findings and the collective experience of the authors, we present the demographic, clinical, and radiographic factors that underlie OC instability, which we hope will serve as components of a grading system in the future. We considered various clinical and radiographic findings including: (1) the mechanism of injury, (2) the patient’s age, (3) CT/CT angiography of head and neck findings and parameters, (4) MRI findings, and (5) neurological exam, for the purpose of determining the severity of the OCDI and offering treatment guidelines based on the summative risk of underlying OC instability. Key Messages: OCDI is a potentially devastating injury, especially in children. Although missing the diagnosis can have potentially catastrophic consequences, reverting to surgical fixation in less severe cases can subject children to unnecessary operative risk and permanently reduce their range of motion. After reviewing all the available reports of pediatric traumatic OCDI in the neurosurgical literature, we propose an outline of clinical and radiographic factors influencing underlying OC instability that could be incorporated into a grading scale to guide treatment. We hope this study stimulates discussion on the standardization of treatment for pediatric OCDI.

OBJECTIVEThe 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.METHODSThe 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.RESULTSAll 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.CONCLUSIONSThe 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.

OBJECTIVE Sagittal synostosis is the most common form of isolated craniosynostosis. Although some centers have reported extensive experience with this condition, most reports have focused on a single center. In 2017, the Synostosis Research Group (SynRG), a multicenter collaborative network, was formed to study craniosynostosis. Here, the authors report their early experience with treating sagittal synostosis in the network. The goals were to describe practice patterns, identify variations, and generate hypotheses for future research. METHODS All patients with a clinical diagnosis of isolated sagittal synostosis who presented to a SynRG center between March 1, 2017, and October 31, 2019, were included. Follow-up information through October 31, 2020, was included. Data extracted from the prospectively maintained SynRG registry included baseline parameters, surgical adjuncts and techniques, complications prior to discharge, and indications for reoperation. Data analysis was descriptive, using frequencies for categorical variables and means and medians for continuous variables. RESULTS Two hundred five patients had treatment for sagittal synostosis at 5 different sites. One hundred twenty-six patients were treated with strip craniectomy and 79 patients with total cranial vault remodeling. The most common strip craniectomy was wide craniectomy with parietal wedge osteotomies (44%), and the most common cranial vault remodeling procedure was total vault remodeling without forehead remodeling (63%). Preoperative mean cephalic indices (CIs) were similar between treatment groups: 0.69 for strip craniectomy and 0.68 for cranial vault remodeling. Thirteen percent of patients had other health problems. In the cranial vault cohort, 81% of patients who received tranexamic acid required a transfusion compared with 94% of patients who did not receive tranexamic acid. The rates of complication were low in all treatment groups. Five patients (2%) had an unintended reoperation. The mean change in CI was 0.09 for strip craniectomy and 0.06 for cranial vault remodeling; wide craniectomy resulted in a greater change in CI in the strip craniectomy group. CONCLUSIONS The baseline severity of scaphocephaly was similar across procedures and sites. Treatment methods varied, but cranial vault remodeling and strip craniectomy both resulted in satisfactory postoperative CIs. Use of tranexamic acid may reduce the need for transfusion in cranial vault cases. The wide craniectomy technique for strip craniectomy seemed to be associated with change in CI. Both findings seem amenable to testing in a randomized controlled trial.

OBJECTIVE Scoliosis is common in patients with Chiari malformation type I (CM-I)–associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.

BACKGROUND: Multimodal analgesia (MMA) may reduce opioid use after surgery for Chiari malformation type I. An MMA protocol was implemented after both posterior fossa decompression without dural opening (PFD) and posterior fossa decompression with duraplasty (PFDD). METHODS: Scheduled nonsteroidal antiinflammatory drugs (ketorolac or ibuprofen) and diazepam were alternated with acetaminophen, and as-needed oxycodone or intravenous morphine. The primary outcome was total opioid requirement over postoperative days 0 to 2. RESULTS: From 2012 to 2017, 49 PFD and 29 PFDD procedures were performed, and 46 of 78 patients used the protocol. Patients with PFD required less opioids than patients with PFDD. Among patients with PFDD, patients with MMA protocol usage had a lower mean opioid requirement than patients with no MMA protocol usage (0.53 ± 0.49 mgEq/kg versus 1.4 ± 1.0 mgEq/kg, P = .0142). In multivariable analysis, MMA protocol usage status independently predicted a mean decrease in opioid requirement of 0.146 mg equivalents/kg (P = .0497) after adjustment for procedure and surgeon. Statistically significant differences were not demonstrated in antiemetic requirements, discharge opioid prescriptions, total direct cost, and length of stay. CONCLUSIONS: A protocol of scheduled nonsteroidal antiinflammatory drugs alternating with scheduled acetaminophen and diazepam was associated with opioid use reductions.

Introduction Endoscope-assisted craniectomy and spring-assisted cranioplasty with post-surgical helmet molding are minimally invasive alternatives to the traditional craniosynostosis treatment of open cranial vault remodeling. Families are often faced with deciding between techniques. This study aimed to understand providers' practice patterns in consulting families about surgical options. Methods An online survey was developed and distributed to 31 providers. The response rate was 84% (26/31). Results Twenty-six (100%) respondents offer a minimally invasive surgical option for sagittal craniosynostosis, 21 (81%) for coronal, 20 (77%) for metopic, 18 (69%) for lambdoid, and 12 (46%) for multi-suture. Social issues considered in determining whether to offer a minimally invasive option include anticipated likelihood of compliance (23 = 88%), distance traveled for care (16 = 62%) and financial considerations (6 = 23%). Common tools to explain options include verbal discussion (25 = 96%), 3D reconstructed CT scans (17 = 65%), handouts (13 = 50%), 3D models (12 = 46%), hand drawings (11 = 42%) and slides (10 = 38%). Some respondents strongly (7 = 27%) or somewhat (3 = 12%) encourage a minimally invasive option over open repair. Others indicate they remain neutral (7 = 27%) or tailor their approach to meet perceived needs (8 = 31%). One (4%) somewhat encourages open repair. Despite this variation, all completely (17 = 65%), strongly (5 = 19%) or somewhat agree (4 = 15%) they use shared decision making in presenting surgical options. Conclusion This survey highlights the range of practice patterns in presenting surgical options to families and reveals possible discrepancies in the extent providers believe they use shared decision making and the extent it is actually used.

Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.

Spasticity in patients with cerebral palsy is a common problem and leads to pain and development of orthopedic impairments as a patient ages. There are a multitude of options both surgical and nonsurgical that are currently utilized to help control spasticity in an attempt to prevent the known consequences on growth. This chapter overviews spasticity, how to assess it, and how to manage it through oral medications, local injections, and surgical interventions including intrathecal baclofen and selective dorsal rhizotomy.

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

OBJECTIVES: Multimodal analgesia (MMA) may reduce opioid use among children who are hospitalized, and may contribute toward enhanced recovery after selective dorsal rhizotomy (SDR) for patients with spasticity in pediatric cerebral palsy. In this retrospective cohort study, we assess an MMA protocol consisting of scheduled nonsteroidal antiinflammatory drug doses (ketorolac or ibuprofen), alternating with scheduled acetaminophen and diazepam doses, with as-needed opioids. It was hypothesized that protocol use would be associated with reductions in opioid requirements and other clinical improvements. METHODS: Data were obtained for 52 patients undergoing SDR at an academic tertiary care pediatric hospital (2012–2017, with the protocol implemented in 2014). Using a retrospective cohort design, we compared outcomes between protocol and nonprotocol patients, employing both univariate t test and Wilcoxon rank test comparisons as well as multivariable regression methods. The primary outcome was total as-needed opioid requirements over postoperative days (PODs) 0 to 2, measured in oral morphine milligram equivalents per kilogram. Additional outcomes included antiemetic medication doses, discharge opioid prescriptions, total direct cost, and length of stay. RESULTS: Twelve patients received the MMA protocol, and 40 patients did not. POD-0 MMA initiation was independently associated with a reduction of 0.14 morphine milligram equivalents per kilogram in mean opioid requirements over PODs 0 to 2 in the multiple regression analysis (95% confidence interval 0.01 to 0.28; P = .04). No statistically significant differences were demonstrated in doses of antiemetic medications, discharge opioid prescriptions, total direct cost, and length of stay. CONCLUSIONS: This MMA protocol may help reduce opioid use after SDR. Improving protocol implementation in a prospective, multisite study will help elucidate further MMA effects on pain, costs, and recovery.

Traumatic perforations of the esophagus and trachea are devastating injuries that necessitate prompt treatment. Large defects benefit from coverage with well vascularized tissue. Injuries at the level of the thoracic inlet are more challenging, as the options for local tissue coverage are limited.This report describes the case of a 24-year-old male who suffered gunshot wounds to his neck resulting in right posterolateral tracheal perforation as well as esophageal perforation at the level of the thoracic inlet. Bronchoscopy and esophagogastroduodenoscopy showed injury of the trachea at 19 cm from the incisors and 2 large defects of the anterior and posterior esophagus at 26 cm. The esophageal defects were temporized with a stent at a first stage. Plastic surgery team was then consulted for flap coverage of the defects.The thoracic team exposed the tracheal and esophageal perforations with a j-type incision of the neck, extending to the sternal notch, and the esophageal stent was removed. The 2 muscles, sternohyoid (SH) and sternothyroid (ST), were dissected free and were inferiorly rotated after they were disinserted superiorly. The SH was placed between the trachea and the esophagus, and the ST between the esophagus and the spine.Postoperative, the patient was receiving nutrition via a gastrostomy tube. An esophagogram was performed on postoperative day (POD) # 7, which showed no esophageal leak. Postoperative diet was started and the patient was discharged on POD# 10 in a good condition. Twelve months postoperative, his wounds were found to be intact, and had no trouble either with breathing or swallowing. LEVEL OF EVIDENCE:: V.

METHODS Through the Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium we accumulated preoperative MRIs and tumor RNA for 50 unique ACP patients. MRIs were assessed quantitatively for 28 different features and analyzed using Multiple Factor Analysis (MFA) and optimal clustering was determined via maximization of Bayesian Information Criterion (BIC). Following bulk RNAseq, differential expression and pathway enrichment were performed using standard methodologies (i.e., DESeq2 and GSEA). RESULTS MRI features were well represented in the first 3 dimensions of MFA (variance explained=67.32%); specifically tumor/cyst size, ventricular size, and cyst fluid diffusivity. Using this three-way axis, we identified 3 patient subgroups. Transcriptional differences between these subgroups indicated one group was enriched for DNA damage response and MYC related pathways, one group enriched for SHH, and one group enriched for WNT/β-catenin and EMT-related pathways. CONCLUSION This preliminary work suggests that there may be unique gene expression variants within ACP, which may be identified preoperatively using easily quantifiable MRI parameters. These radiogenomic signatures could provide prognostic information and/or guidance in the selection of antitumor therapies for children with ACP.

Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions.

This article addresses the key features, clinical presentation, patterns of injury, indicated workup, and radiographic findings associated with craniocervical injuries in the pediatric population. It discusses nonsurgical and surgical management of pediatric cervical spine trauma, addressing when each is indicated, and the various techniques available to the pediatric neurosurgeon.

Background: Surgical site infections (SSIs) are one of the most common complications following pediatric complex tethered spinal cord release. This patient population is similar in some ways to the neuromuscular scoliosis population, in which higher-than-expected rates of gram-negative SSIs have been identified. Methods: We conducted a single-center retrospective chart review of all patients who underwent complex tethered spinal cord release over a 10-year period between 2007 and 2017. Results: A total of 69 patients were identified, with 10 documented SSIs (14%). 50% of the SSIs were polymicrobial or included at least 1 gram-negative organism. Among the organisms isolated, 3 were fully or ­partially resistant to cefazolin, the most common antibiotic prophylaxis in this population. Conclusion: Among children undergoing complex tethered spinal cord release, gram-negative and polymicrobial infections are a significant cause of SSIs. Although further multicenter data are needed, these findings suggest that standard antibiotic prophylaxis with cefazolin may not be sufficient.

Pediatric spinal trauma is a broad topic with nuances specific to each anatomic region of the spinal column. The purpose of this report is to provide a brief review highlighting the most important and common clinical issues regarding the diagnosis and management of pediatric spine trauma. Detailed descriptions of imaging findings along with specific operative and nonoperative management of each fracture and dislocation type are beyond the scope of this review.

Children with myelomeningocele (MMC) are at increased risk of developing neuromuscular scoliosis and spinal cord re-tethering (Childs Nerv Syst 12:748-754, 1996; Neurosurg Focus 16:2, 2004; Neurosurg Focus 29:1, 2010). Some centers perform prophylactic untethering on asymptomatic MMC patients prior to scoliosis surgery because of concern that additional traction on the cord may place the patient at greater risk of neurologic deterioration peri-operatively. However, prophylactic untethering may not be justified if it carries increased surgical risks. The purpose of this study was to determine if prophylactic untethering is necessary in asymptomatic children with MMC undergoing scoliosis surgery. A multidisciplinary, retrospective cohort study from seven children’s hospitals was performed including asymptomatic children with MMC

OBJECTIVEHypermobility of the craniocervical junction (CCJ) in patients with Down syndrome (DS) is common. Whereas atlantoaxial (C1–2) hypermobility is well characterized, occipitoatlantal (Oc–C1) laxity is recognized but poorly defined. A clear understanding of the risks associated with DS-related hypermobility is lacking. Research efforts to address the topic of axial cervical spine instability in the patient with DS require a reliable and reproducible means of assessing CCJ mobility. The authors conducted a pilot study comparing two methods of quantifying motion of the CCJ on dynamic (flexion/extension) plain radiographs: the delta–condyle-axial interval (ΔCAI) and the delta–basion-axial interval (ΔBAI) methods.METHODSDynamic radiographs from a cohort of 10 patients with DS were evaluated according to prescribed standards. Independent movement of Oc–C1, C1–2, and Oc–C2 was calculated. Interrater and intrarater reliability for CCJ mobility was then calculated for both techniques.RESULTSMeasurement using the ΔCAI technique had excellent fidelity with intraclass correlation coefficients (ICCs) of 0.77, 0.71, and 0.80 for Oc–C1, C1–2, and Oc–C2, respectively. The ΔBAI technique had lower fidelity, yielding respective ICCs of 0.61, 0.65, and 0.50.CONCLUSIONSThis pilot study suggests that ΔCAI is a superior measurement technique compared to ΔBAI and may provide reliable assessment of the mobility of the CCJ on dynamic radiographs in the pediatric patient with DS. The use of reliable and reproducible measurement techniques strengthens the validity of research derived from pooled database efforts.

OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

Syrinx has been reported in 25–85 % of children with Chiari malformation type I (CMI), and it is most commonly cervical in location. As a result, cervical MRI is routinely included in an evaluation for CMI. Isolated thoracic syrinx without involvement of the cervical cord in this population is uncommon but clinically important because its presence may influence the decision to operate, surgical techniques employed, or interpretation of follow-up imaging. The purpose of this study was to determine the incidence of isolated thoracic syrinx in a large group of children evaluated for CMI. We retrospectively reviewed all patients under 21 years of age who were evaluated for CMI at Columbia University/Morgan Stanley Children’s Hospital of New York from 1998 to 2013. All patients underwent MRI of the entire spine as part of the CMI evaluation, regardless of whether surgery was planned. The proportion of patients exhibiting isolated thoracic syrinx was determined. Presenting signs, symptoms, and imaging findings were then studied in an attempt to identify any clinical features associated with isolated thoracic syrinx. We identified 266 patients evaluated over the study period. One-hundred thirty-two patients (50 %) presented with a syrinx, and 12 patients (4.5 % of all patients evaluated and 9.1 % of all patients with a syrinx) had an isolated thoracic syrinx. Demographic variables, clinical presentation, and extent of tonsillar ectopia showed great heterogeneity in this group, and no factor was consistently associated with isolated thoracic syrinx. Isolated thoracic syrinx is an uncommon but clinically significant finding in children with CMI. Our data demonstrate that the presence of a CMI-related thoracic syrinx cannot be reliably predicted clinically and is therefore likely to be missed in patients who do not undergo complete spinal cord imaging. MRI of the entire spinal cord should be considered for all children undergoing initial evaluation for CMI.

OBJECTThe long-term consequences of atlantoaxial (AA) and occipitocervical (OC) fusion and instrumentation in young children are unknown. Anecdotal reports have raised concerns regarding altered growth and alignment of the cervical spine after surgical intervention. The purpose of this study was to determine the long-term effects of these surgeries on the growth and alignment of the maturing spine.METHODSA multiinstitutional retrospective chart review was conducted for patients less than or equal to 6 years of age who underwent OC or AA fusion with rigid instrumentation at 9 participating centers. All patients had at least 3 years of clinical and radiographic follow-up data and radiographically confirmed fusion. Preoperative, immediate postoperative, and most recent follow-up radiographs and/or CT scans were evaluated to assess changes in spinal growth and alignment.RESULTSForty children (9 who underwent AA fusion and 31 who underwent OC fusion) were included in the study (mean follow-up duration 56 months). The mean vertical growth over the fused levels in the AA fusion patients represented 30% of the growth of the cervical spine (range 10%–50%). Three different vertical growth patterns of the fusion construct developed among the 31 OC fusion patients during the follow-up period: 1) 16 patients had substantial growth (13%–46% of the total growth of the cervical spine); 2) 9 patients had no meaningful growth; and 3) 6 patients, most of whom presented with a distracted atlantooccipital dislocation, had a decrease in the height of the fused levels (range 7–23 mm). Regarding spinal alignment, 85% (34/40) of the patients had good alignment at follow-up, with straight or mildly lordotic cervical curvatures. In 1 AA fusion patient (11%) and 5 OC fusion patients (16%), we observed new hyperlordosis (range 43°–62°). There were no cases of new kyphosis or swan-neck deformity, evidence of subaxial instability, or unintended subaxial fusion. No preoperative predictors of these growth patterns or alignment were evident.CONCLUSIONSThese results demonstrate that most young children undergoing AA and OC fusion with rigid internal fixation continue to have good cervical alignment and continued growth within the fused levels during a prolonged follow-up period. However, some variability in vertical growth and alignment exists, highlighting the need to continue close long-term follow-up.

STUDY DESIGN Multicenter retrospective cohort study with multivariate analysis. OBJECTIVE To determine factors predictive of posterior atlantoaxial fusion failure in pediatric patients. SUMMARY OF BACKGROUND DATA Fusion rates for pediatric posterior atlantoaxial arthrodesis have been reported to be high in single-center studies; however, factors predictive of surgical non-union have not been identified by a multicenter study. METHODS Clinical and surgical details for all patients who underwent posterior atlantoaxial fusion at seven pediatric spine centers from 1995 to 2014 were retrospectively recorded. The primary outcome was surgical failure, defined as either instrumentation failure or fusion failure seen on either plain x-ray or computed tomography scan. Multiple logistic regression analysis was undertaken to identify clinical and technical factors predictive of surgical failure. RESULTS One hundred thirty-one patients met the inclusion criteria and were included in the analysis. Successful fusion was seen in 117 (89%) of the patients. Of the 14 (11%) patients with failed fusion, the cause was instrumentation failure in 3 patients (2%) and graft failure in 11 (8%). Multivariate analysis identified Down syndrome as the single factor predictive of fusion failure (odds ratio 14.6, 95% confidence interval [3.7-64.0]). CONCLUSION This retrospective analysis of a multicenter cohort demonstrates that although posterior pediatric atlantoaxial fusion success rates are generally high, Down syndrome is a risk factor that significantly predicts the possibility of surgical failure. LEVEL OF EVIDENCE 3.

Magnetic resonance imaging (MRI) captures the three dimensional way in which tumors are organized in the breast, defined as imaging phenotypes in the I-SPY 1 trial. We developed a gene set based on the way in which breast epithelial cells aggregate and organize in three dimensional cultures. We investigated whether these organizational genes correspond to the imaging phenotypes. MRI phenotypes have been shown to correspond to the degree of response to neoadjuvant chemotherapy, and are used to predict the ability to achieve breast conservation treatment (Mukhtar et al, Ann Surg Oncol, 20: 3823–3830, 2013). We hypothesized that the molecular profile accompanying phenotypic changes occurring during the organization process of non-malignant acini may explain the molecular basis of MRI tumor phenotypes. We have developed prediction models for MRI phenotypes based on expression profiles identified during the organization process of non-malignant breast epithelial cells in three-dimensional laminin-rich extracellular matrix (Fournier et al. Cancer Res, 66, 7095-102, 2006). We analyzed a subset of 324 organizational genes in 147 samples from stage II-III breast cancer in the I-SPY 1 trial cohort with Agilent microarrays and MRI annotation (CALGB 150007/150012; ACRIN 6657). MRI phenotype of the index lesion was assessed by the site radiologists using the following radiographic criteria: A) well defined unicentric mass; B) well-defined multilobulated mass; C) area enhancement with nodularity; D) area enhancement without nodularity; E) Septal spreading. The distribution of phenotypes in I-SPY 1 was: A: 16%, B: 33%, C: 30%, D: 15%, E: 7%. We developed predictors for MRI phenotypes dichotomized as either "well-defined" (A and B) or "non-well-defined" (C, D and E). Using patent-pending algorithms we selected a subset of the organizational genes with the greatest predictive power to identify MRI "well-defined" phenotypes in the I-SPY 1 cohort. Then prediction models were developed using the 50 top ranking genes and logistic regression methods. We followed Monte-Carlo cross validation method to make sure that the performance of a model is not a result of over-fitting the model to the sample data using separate datasets to support the modeling. The samples were randomly partitioned 10,000 times in a 85% training, and 15% test ratio to test models performance. The resulting performance of predictive models in the test set had an average classification accuracy of greater than 80% (ROC statistics AUC>0.8) using gene expression measurements from between 16 to 20 genes. For random lists of 16-20 genes, the accuracy was approximately 50% (ROC AUC∼0.5). Amongst the MRI models were several genes that are known to regulate key cellular pathways such as cell division, metabolism, and migration using MetaCore pathway analysis. Taken together, the results suggest that the MRI phenotypes may be a manifestation of the organization genes that determine behavior in three dimensional culture. Future research includes confirming these results using an independent dataset, defining the potential drivers of MRI phenotypes, and determining if putative drivers provide a key contribution to tumor subtypes. Citation Format: Marcia V Fournier, Alan Derr, Alex Margulis, Kevin Reid, Sara Brumbaugh, Richard Anderson, W Fraser Symmans, Laura Esserman, Nola Hylton. Gene expression profiles accompanying phenotypic changes during non-malignant breast epithelial cells acini formation to explain MRI phenotypes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-19.

When it comes to library collections, it is critical that we not confuse means with ends. The purpose of the library is not to have a great collection; the purpose of the library is to meet the teaching, learning, and research needs of those it was established to serve. The collection is a tool that we use in pursuit of that goal, but it is not the only tool, and the collection itself is certainly not the goal. One problem with building collections (as traditionally understood) is that it involves guesswork, trying to guess ahead of time which exact books, journals, and databases our users will need. But inevitably, we guess wrong. We are very good at selecting relevant and high-quality books but not very good at selecting the exact titles that our patrons will need. So in many libraries, we have been moving aggressively in the direction of what is called patron-driven or demand-driven acquisition: We put records in the catalog for electronic books that we have not yet purchased, and purchase is driven by the actual use of those books. Even better, the process of purchase is completely transparent to the patron, so the only thing the patron experiences is access to a much larger collection of titles than we could possibly offer by preemptive purchase. The result is not likely to be a better collection (in terms of coherence and completeness), but if the result is that our patrons are better able to do their teaching, learning, and research, then many librarians will consider that to be an acceptable tradeoff. The model that built the great research collections was a reflection of the limitations of the print world. When print runs for scholarly monographs were modest and moving individual books from one institution to another was time …

Background Fusion rates following rigid internal instrumentation for occipitocervical and atlantoaxial instability approach 100% in many reports. Based on this success and the morbidity that can be associated with obtaining autograft for fusion, surgeons increasingly select alternative graft materials. Objective To examine fusion failure using various graft materials in a retrospective observational study. Methods Insurance claims databases (Truven Health MarketScan® [Truven Health Analytics, Ann Arbor, Michigan] and IMS Health Lifelink/PHARMetrics [IMS Health, Danbury, Connecticut]) were used to identify patients with CPT codes 22590 and 22595. Patients were divided by age (≥18 yr = adult) and arthrodesis code, establishing 4 populations. Each population was further separated by graft code: group 1 = 20938 (structural autograft); group 2 = 20931 (structural allograft); group 3 = other graft code (nonstructural); group 4 = no graft code. Fusion failure was assigned when ≥1 predetermined codes presented in the record ≥90 d following the last surgical procedure. Results Of 522 patients identified, 419 were adult and 103 were pediatric. Fusion failure occurred in 10.9% (57/522) of the population. There was no statistically significant difference in fusion failure based on graft material. Fusion failure occurred in 18.9% of pediatric occipitocervical fusions, but in 9.2% to 11.1% in the other groups. Conclusion Administrative data regarding patients who underwent instrumented occipitocervical or atlantoaxial arthrodesis do not demonstrate differences in fusion rates based on the graft material selected. When compared to many contemporary primary datasets, fusion failure was more frequent; however, several recent studies have shown higher failure rates than previously reported. This may be influenced by broad patient selection and fusion failure criteria that were selected in order to maximize the generalizability of the findings.

The early principles of spinal fusion in the adolescent population focused on preventing progression while simultaneously correcting the spinal deformity. These principles have remained relatively unchanged since their introduction more than a century ago, but recent improvements in imaging, instrumentation, and corrective techniques have provided new insight on the diagnosis, management, and postoperative care of this condition. Treatment options for the management of patients with early onset scoliosis have also evolved dramatically over the last 2 decades. Further knowledge on the physiology of lung development and the detrimental effects of early fusion in the early onset scoliosis population has led to the development of growth friendly implants and other surgical techniques that allow correction of the deformity while maintaining spine, lung, and chest wall development. The following is an overview of current techniques on the management of adolescent idiopathic and early onset scoliosis to help provide guidance on the available surgical alternatives to address these conditions.

Study Design Consensus-building using the Delphi and nominal group technique. Objective To establish best practice guidelines using formal techniques of consensus building among a group of experienced spinal deformity surgeons to avert wrong-level spinal deformity surgery. Summary of Background Data Numerous previous studies have demonstrated that wrong-level spinal deformity occurs at a substantial rate, with more than half of all spine surgeons reporting direct or indirect experience operating on the wrong levels. Nevertheless, currently, guidelines to avert wrong-level spinal deformity surgery have not been developed. Methods The Delphi process and nominal group technique were used to formally derive consensus among 16 fellowship-trained spine surgeons. Surgeons were surveyed for current practices, presented with the results of a systematic review, and asked to vote anonymously for or against item inclusion during three iterative rounds. Agreement of 80% or higher was considered consensus. Items near consensus (70% to 80% agreement) were probed in detail using the nominal group technique in a facilitated group meeting. Results Participants had a mean of 13.4 years of practice (range: 2–32 years) and 103.1 (range: 50–250) annual spinal deformity surgeries, with a combined total of 24,200 procedures. Consensus was reached for the creation of best practice guidelines (BPGs) consisting of 17 interventions to avert wrong-level surgery. A final checklist consisting of preoperative and intraoperative methods, including standardized vertebral-level counting and optimal imaging criteria, was supported by 100% of participants. Conclusion We developed consensus-based best practice guidelines for the prevention of wrong-vertebral-level surgery. This can serve as a tool to reduce the variability in preoperative and intraoperative practices and guide research regarding the effectiveness of such interventions on the incidence of wrong-level surgery. Level of Evidence Level V.

INTRODUCTION: Whole exome sequencing (WES) of newly diagnosed pediatric central nervous system (CNS) tumors is quickly becoming part of routine care. Through the Precision in Pediatric Sequencing (PiPseq) program at Columbia University, we have found potentially actionable mutations in more than 40% of evaluable CNS cases at diagnosis. More recently, we have integrated this approach into the management of patients undergoing surgery for CNS tumor recurrence. METHOD: After obtaining informed consent, tumor-normal WES with transcriptome analysis was performed in a CLIA-certified laboratory on fresh frozen or paraffin embedded CNS tumor samples and peripheral blood. RESULTS: 7 cases (5 male, 2 female; median age 5 years) with adequate diagnostic and recurrent tumor tissue were tested. No case had a somatic mutation of established clinical utility (tier 1). Among 3 embryonal tumors, a splice site variant in TSC1 (tier 2 mutation of potential utility) was detected in a medulloblastoma, but only at recurrence and not at initial diagnosis. FOXR2 overexpression was detected at diagnosis and confirmed at early progression of a temporal lobe tumor, prompting revision of the initial diagnosis of high grade glioma to CNS neuroblastoma subtype of PNET, and treated accordingly. In a third patient initially diagnosed with medulloblastoma, overexpression of PDGFRA, MDM4, CDKN2A, EGFR, OLIG2, and GFAP supported a change in diagnosis to glioblastoma. Two gliomas had tier 2 mutations detected at initial diagnosis and progression: SETD2 p.R2040* (optic nerve lesion, called pseudotumor initially but glioma at progression), and H3F3A p.K28M (thalamic low grade glioma). In one patient with ependymoma, copy number gain of 1q25 (associated with poor prognosis) was seen only in the recurrence specimen. CONCLUSION: Our preliminary experience suggests that in pediatric CNS tumor patients referred for reoperation at recurrence, repeat WES may reveal a previously unrecognized treatment option, at least in embryonal tumors.

Object The significance of draining vein anatomy is poorly defined in pediatric arteriovenous malformations (AVMs). In adult cohorts, the presence of fewer veins has been shown to lead to an increased rate of hemorrhage, but this phenomenon has not yet been studied in pediatric AVMs. This report analyzes the impact of draining vein anatomy on presentation and outcome in a large series of pediatric AVMs. Methods Eighty-five pediatric patients with AVMs were treated at the Columbia University Medical Center between 1991 and 2012. Charts were retrospectively reviewed for patient characteristics, clinical course, neurological outcome, and AVM angioarchitectural features identified on the angiogram performed at presentation. Univariate analyses were performed using chi-square test and ANOVA when appropriate; multivariate analysis was performed using logistic regression. Results Four patients were excluded due to incomplete records. Twenty-seven patients had 2 or 3 draining veins; 12 (44.4%) of these patients suffered from hemorrhage prior to surgery. Fifty-four patients had 1 draining vein; 39 (72.2%) of these 54 suffered from hemorrhage. Independent predictors of hemorrhage included the presence of a single draining vein (p = 0.04) and deep venous drainage (p = 0.02). Good outcome (modified Rankin Scale [mRS] score < 3) on discharge was found to be associated with higher admission Glasgow Coma Scale (GCS) scores (p = 0.0001, OR 0.638, 95% CI 0.40–0.93). Poor outcome (mRS score > 2) on discharge was found to be associated with deep venous drainage (p = 0.04, OR 4.68, 95% CI 1.1–19.98). A higher admission GCS score was associated with a lower discharge mRS score (p = 0.0003, OR 0.6, 95% CI 0.46–0.79), and the presence of a single draining vein was associated with a lower mRS score on long-term follow-up (p = 0.04, OR 0.18, 95% CI 0.032–0.99). Conclusions The authors' data suggest that the presence of a single draining vein or deep venous drainage plays a role in hemorrhage risk and ultimate outcome in pediatric AVMs. Small AVMs with a single or deep draining vein may have the highest risk of hemorrhage.

Object Randomized clinical trials have established that lumbar selective dorsal rhizotomy (SDR) reduces lower-extremity tone and improves functional outcome in children with spastic cerebral palsy. Significant data exist to support a secondary effect on upper-extremity function in patients with upper-extremity spasticity. The effects of SDR on upper-extremity tone, however, are not well characterized. In this report, the authors sought to assess changes in upper-extremity tone in individual muscle groups after SDR and tried to determine if these changes could be predicted preoperatively. Methods The authors retrospectively reviewed 42 children who underwent SDR at Columbia University Medical Center/Morgan Stanley Children's Hospital of NewYork-Presbyterian between 2005 and 2011. Twenty-five had upper-extremity spasticity. All underwent pre- and postoperative examination for measuring tone (Modified Ashworth Scale) and assessing functional outcome. Follow-up examinations with therapists were performed at least once at a minimum of 2 months postoperatively (mean 15 months). Results In the upper extremities, 23 (92%) of 25 patients had improvements of at least 1 Ashworth point in 2 or more independent motor groups on the Modified Ashworth Scale, and 12 (71%) of 17 families surveyed reported increases in motor control or spontaneous movement. The mean Modified Ashworth Scale scores for all upper-extremity muscle groups demonstrated an improvement from 1.34 to 1.22 (p < 0.001). Patients with a mean preoperative upper-extremity tone of 1.25–1.75 were most likely to benefit from reduction in tone (p = 0.0019). Proximal and pronator muscle groups were most likely to demonstrate reduced tone. Conclusions In addition to improvements in lower-extremity tone and function, SDR has demonstrable effects on upper extremities. Greater than 90% of our patients with elevated upper-extremity tone demonstrated reduction in tone in at least 2 muscle groups postoperatively. Patients with a mean Modified Ashworth Scale upper-extremity score of 1.25–1.75 may encounter the greatest reduction in upper-extremity tone.

The Pediatric Anesthesia Neuro Development Assessment (PANDA) team at the Anesthesiology Department at Columbia University Medical Center held its fifth biennial symposium to discuss issues regarding potential neurotoxicity of anesthetic agents in pediatric patients. Overall optimal surgical timing as well as a "critical window" for surgery on a specialty specific basis are areas of focus for the American Academy of Pediatrics Surgical Advisory Panel. An ad hoc panel of pediatric surgical experts representing general surgery, urology, neurosurgery, and ophthalmology was assembled for this meeting and provided a dialogue focused on the benefits of early intervention versus potential anesthetic risk, addressing parental concerns, and the need for continued interdisciplinary collaboration in this area.

CR-11. PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA CYST FLUID DEMONSTRATES A PRO-INFLAMMATORY MILIEU Andrew Donson2, Andrea Griesinger2, Vladimir Amani2, Richard C.E. Anderson4, Toba N. Niazi3, Michael H. Handler1,2, Nicholas K. Foreman1,2, and Todd C. Hankinson1,2; Children’s Hospital Colorado, Aurora, CO, USA; University of Colorado School of Medicine, Aurora, CO, USA; Nicklaus Children’s Hospital, Miami, FL, USA; Morgan Stanley Children’s Hospital of New York-Presbyterian, New York, NY, USA BACKGROUND: The cyst component of pediatric adamantinomatous craniopharyngioma (ACP) often exerts substantial mass effect, grows unpredictably, and is poorly responsive to radiation therapy. Current cyst-directed therapies mandate surgical intervention. An improved understanding of the drivers of ACP cyst growth may allow for the identification of systemic therapies that can control cyst expansion and improve tumor control and/or our ability to safely undertake radical tumor resection. METHODS: Milliplex cytokine expression analysis was used to compare the cytokine milieu of ACP cyst (n 1⁄4 5) to another common cyst generating pediatric brain tumor, Juvenile Pilocytic Astrocytoma (JPA, n 1⁄4 5). The ratio of cytokine levels in the 2 tumor types was compared. RESULTS: Compared to JPA cysts, all ACP specimens showed a highly pro-inflammatory cytokine pattern. Among the cytokines with elevated expression level ratios in ACP, relative to JPA, were IL-6 (353.9, p 1⁄4 1.23x10); IL-8 (57.6, p 1⁄4 0.04); IL-10 (35.5, p 1⁄4 0.003); TNF-a (8.21, p 1⁄4 0.01); and IL-1b (3.65, p 1⁄4 0.005). CONCLUSIONS: ACP cyst fluid appears to be characterized by a highly pro-inflammatory cytokine expression pattern. Understanding the cellular source of these cytokines and the efficacy of selective cytokine blockade may represent an opportunity for therapeutic intervention. Neuro-Oncology 18:iii18–iii23, 2016. doi:10.1093/neuonc/now068.11 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

OBJECTIVE Administrative billing data may facilitate large-scale assessments of treatment outcomes for pediatric Chiari malformation Type I (CM-I). Validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code algorithms for identifying CM-I surgery are critical prerequisites for such studies but are currently only available for adults. The objective of this study was to validate two ICD-9-CM code algorithms using hospital billing data to identify pediatric patients undergoing CM-I decompression surgery. METHODS The authors retrospectively analyzed the validity of two ICD-9-CM code algorithms for identifying pediatric CM-I decompression surgery performed at 3 academic medical centers between 2001 and 2013. Algorithm 1 included any discharge diagnosis code of 348.4 (CM-I), as well as a procedure code of 01.24 (cranial decompression) or 03.09 (spinal decompression or laminectomy). Algorithm 2 restricted this group to the subset of patients with a primary discharge diagnosis of 348.4. The positive predictive value (PPV) and sensitivity of each algorithm were calculated. RESULTS Among 625 first-time admissions identified by Algorithm 1, the overall PPV for CM-I decompression was 92%. Among the 581 admissions identified by Algorithm 2, the PPV was 97%. The PPV for Algorithm 1 was lower in one center (84%) compared with the other centers (93%–94%), whereas the PPV of Algorithm 2 remained high (96%–98%) across all subgroups. The sensitivity of Algorithms 1 (91%) and 2 (89%) was very good and remained so across subgroups (82%–97%). CONCLUSIONS An ICD-9-CM algorithm requiring a primary diagnosis of CM-I has excellent PPV and very good sensitivity for identifying CM-I decompression surgery in pediatric patients. These results establish a basis for utilizing administrative billing data to assess pediatric CM-I treatment outcomes.

OBJECTIVE Chiari malformation Type I (CM-I) is a common and often debilitating pediatric neurological disease. However, efforts to guide preoperative counseling and improve outcomes research are impeded by reliance on small, single-center studies. Consequently, the objective of this study was to investigate CM-I surgical outcomes using population-level administrative billing data. METHODS The authors used Healthcare Cost and Utilization Project State Inpatient Databases (SID) to study pediatric patients undergoing surgical decompression for CM-I from 2004 to 2010 in California, Florida, and New York. They assessed the prevalence and influence of preoperative complex chronic conditions (CCC) among included patients. Outcomes included medical and surgical complications within 90 days of treatment. Multivariate logistic regression was used to identify risk factors for surgical complications. RESULTS A total of 936 pediatric CM-I surgeries were identified for the study period. Overall, 29.2% of patients were diagnosed with syringomyelia and 13.7% were diagnosed with scoliosis. Aside from syringomyelia and scoliosis, 30.3% of patients had at least 1 CCC, most commonly neuromuscular (15.2%) or congenital or genetic (8.4%) disease. Medical complications were uncommon, occurring in 2.6% of patients. By comparison, surgical complications were diagnosed in 12.7% of patients and typically included shunt-related complications (4.0%), meningitis (3.7%), and other neurosurgery-specific complications (7.4%). Major complications (e.g., stroke or myocardial infarction) occurred in 1.4% of patients. Among children with CCCs, only comorbid hydrocephalus was associated with a significantly increased risk of surgical complications (OR 4.5, 95% CI 2.5–8.1). CONCLUSIONS Approximately 1 in 8 pediatric CM-I patients experienced a surgical complication, whereas medical complications were rare. Although CCCs were common in pediatric CM-I patients, only hydrocephalus was independently associated with increased risk of surgical events. These results may inform patient counseling and guide future research efforts.

Stereotactic radiosurgery (SRS) is an evolving approach for the treatment of pediatric neurovascular disease. Since its first use in the treatment of an arteriovenous malformation (AVM) in 1970, it has been used safely and effectively in treating adult patients with AVMs, selected cerebral cavernous malformations (CCM), and arteriovenous fistulas (AVF). More recently, several case series have shown expansion to the pediatric population that have yielded promising results, with SRS achieving total obliteration of AVMs in up to 90 % of patients. The benefits of SRS are likely greatest in lesions that are deep-seated or adjacent to eloquent cortex, where the risks of microsurgery are typically greater than the risks of SRS. The validation of risk scores, which have identified smaller AVM volume and younger age as prognosticators of radiosurgical success, has helped guide patient selection and improve outcomes overall. However, concerns of persistent hemorrhage risk during the latency period prior to obliteration, as well as limited knowledge of long-term, radiation-specific complications, continue to limit the usage of SRS for pediatric neurovascular disease.

Object Idiopathic intracranial hypertension (IIH) may be refractory to available medical and surgical therapies. Patients with this condition may suffer from intractable headaches, experience visual deterioration, or have other symptoms related to elevated intracranial pressure. Internal cranial expansion (ICE) is a novel surgical procedure that the authors have developed for the treatment of patients with this condition. Here, they describe ICE and present their initial experience in using this surgical procedure for the treatment of patients with refractory IIH. Methods The authors conducted a retrospective review of 10 consecutive patients who underwent ICE for the treatment of IIH during a 5-year period. Preoperative and postoperative clinical parameters including patient symptoms, presence of papilledema, and available ICP or CSF opening pressures were compared. Procedural details and complications were noted. Intracranial volume increases were calculated using available pre- and postoperative CT scans. Results Follow-up for the 10 patients in this series ranged from 1 to 39.6 months (mean 15.5 months). Technically successful ICE was performed in all patients within the cohort. Surgical complications included a single postoperative seizure in one patient and a sagittal sinus tear with no clinical sequelae in another patient. At the time of last follow-up, 7 (70%) of 10 patients were either symptomatically improved or asymptomatic. Six (67%) of 9 patients with preoperative headaches had reduction or resolution of this symptom, and all patients (4 of 4) with preoperative papilledema had a reduction in or complete resolution of this sign. Postoperative ICP or CSF opening pressures were normal in all patients (4 of 4) tested. Postoperative intracranial volume expansion ranged between 3.8% and 12%. Conclusions Internal cranial expansion is a safe and effective surgery for the treatment of patients with refractory IIH. This surgery expands the intracranial volume and thus promotes ICP normalization, which may lead to the reduction or complete resolution of the signs and symptoms of IIH. Internal cranial expansion may be used as part of a multidisciplinary management approach in the treatment of refractory IIH.

Haque R, Wojtasiewicz T, Gerrah R, Gilmore L, Saiki Y, Chen JM, Richmond M, Feldstein NA, Anderson RCE. Management of intracranial hemorrhage in a child with a left ventricular assist device. Abstract: Pediatric patients bridged to heart transplant with LVADs require chronic anticoagulation and are at increased risk of hemorrhagic complications, including intracranial hemorrhage. In this population, intracranial hemorrhage is often fatal. We report a case of successful management of a five-yr-old-boy with DCM on an LVAD who developed a subdural hematoma. We initially chose medical management, weighing the patient’s high risk of thromboembolism from anticoagulation reversal against the risk of his chronic subdural hematoma. When head CT showed expansion of the hemorrhage with increasing midline shift, we chose prompt surgical evacuation of the hematoma with partial reversal of anticoagulation, given the increased risk of acute deterioration. The patient ultimately received an orthotopic heart transplant and was discharged with no permanent neurological complications. This represents a case of a pediatric patient on an LVAD who survived a potentially fatal subdural hematoma and was successfully bridged to cardiac transplantation.

Object Conventional cerebral angiography and treatment for ruptured arteriovenous malformations (AVMs) in children are often performed in a delayed fashion. In adults, current literature suggests that AVM-associated aneurysms may be more likely to hemorrhage than isolated AVMs, which often leads to earlier angiography and endovascular treatment of associated aneurysms. The nature of AVM-associated aneurysms in the pediatric population is virtually unknown. In this report, the authors investigate the relationship of associated aneurysms in a large group of children with AVMs. Methods Seventy-seven pediatric patients (≤ 21 years old) with AVMs were treated at the Columbia University Medical Center between 1991 and 2010. Medical records and imaging studies were retrospectively reviewed, and associated aneurysms were classified as arterial, intranidal, or venous in location. Clinical presentation and outcome variables were compared between children with and without AVM-associated aneurysms. Results A total of 30 AVM-associated aneurysms were found in 22 children (29% incidence). Eleven were arterial, 9 intranidal, and 10 were venous in location. There was no significant difference in the rate of hemorrhage (p = 0.91) between children with isolated AVMs (35 of 55 [64%]) and children with AVM-associated aneurysms (13 of 22 [59%]). However, of the 11 children with AVM-associated aneurysms in an arterial location, 10 presented with hemorrhage (91%). An association with hemorrhage was significant in univariate analysis (p = 0.045) but not in multivariate analysis (p = 0.37). Conclusions Associated aneurysms are present in nearly a third of children with AVMs, and when arterially located, are more likely to present with hemorrhage. These data suggest that early angiography with endovascular treatment of arterial-based aneurysms in children with AVMs may be indicated.