Case report: Slipped capital femoral epiphysis: a rare adverse event associated with FGFR tyrosine kinase inhibitor therapy in a child.

We report a case of slipped capital femoral epiphysis (SCFE), an on target skeletal toxicity of a pan-FGFR TKI inhibitor, erdafitinib. A 13-year-old boy was diagnosed to have an optic pathway/hypothalamic glioma with signs of increased intracranial pressure and obstructive hydrocephalus requiring placement of ventriculo-peritoneal (VP) shunt. Sequencing of the tumor showed FGFR1-tyrosine kinase domain internal tandem duplication (FGFR1-KD-ITD). He developed hypothalamic obesity with rapid weight gain and BMI >30. At 12 weeks of treatment with erdafitinib, he developed persistent knee pain. X-ray of the right hip showed SCFE. Erdafitinib was discontinued, and he underwent surgical pinning of the right hip. MRI at discontinuation of erdafitinib showed a 30% decrease in the size of the tumor, which has remained stable at 6 months follow-up. Our experience and literature review suggest that pediatric patients who are treated with pan-FGFR TKIs should be regularly monitored for skeletal side effects.

Prospective Evaluation of Health-Related Quality-of-Life in Children with Craniosynostosis.

OBJECTIVE: To investigate health-related quality of life (HRQL) in children aged 2 to 7 years, who have undergone surgery for craniosynostosis. DESIGN: Cross-sectional survey. SETTING: A tertiary pediatric academic medical center. PARTICIPANTS: Children with craniosynostosis who underwent surgical correction, and who were 2-7 years old at the time of the study. Children from families that did not speak English were excluded. INTERVENTIONS: Caregivers were asked to fill out the Pediatric Quality of Life Inventory (PedsQL) Core Parent Report and the PedsQL Cognitive Functioning Scale. MAIN OUTCOME MEASURES: PedsQL: Psychosocial Health Summary Score, Physical Health Summary Score, Total Core Score, Cognitive Functioning Scale Score. Scores range from 0 to 100, with higher scores reflecting greater QoLSubject factors: comorbidities, syndromic status, type of craniosynostosis, type of surgery. RESULTS: The study included 53 subjects, of whom 13.2% had a syndrome. Core and cognitive scores did not depend on presence of a syndrome or suture involved. Subjects who underwent posterior cranial distraction achieved higher Total Core Scores than subjects who underwent open vault remodeling. Among subjects with sagittal craniosynostosis, there was a tendency for higher scores among children who underwent minimally-invasive surgery compared to those who underwent open vault remodeling. CONCLUSIONS: This study demonstrates similar HRQL among children with and without a syndrome, higher HRQL among children undergoing posterior cranial distraction than those undergoing open vault remodeling, and trends towards higher HRQL in children with sagittal craniosynostosis who underwent minimally-invasive surgery compared to those who underwent open vault remodeling.

Posterior Cranial Distraction in Craniosynostosis: A Systematic Review of the Literature.

OBJECTIVE: Posterior cranial distraction (PCD) is a surgical technique to address craniosynostosis, especially in syndromic patients. The technique has the ability to significantly expand the cranium, while requiring minimal dural dissection, compared to cranial remodeling. Our goals were to determine the patient characteristics and surgical outcomes of PCD. The two questions that we sought to answer were: 1) What is the average published complication rate and the most common complications of PCD? and 2) How much intracranial volume expansion can one expect with PCD? DESIGN: A PubMed database search of articles on PCD was performed. Case reports and articles with overlapping patients were excluded. A systematic review was performed using the remaining articles. MAIN OUTCOME MEASURES: Patient data were extracted in order to determine the total number of patients, patients with a syndrome, types of syndromes, mean age at surgery, mean distraction distance, mean increase in intracranial volume, and complications. RESULTS: 18 articles representing 325 patients were analyzed. A syndrome was present in 68.6% of patients. The mean age at time of surgery was 22.1 months. Mean distraction amount was 24.7 mm. Mean increase in intracranial volume was 253.2 cm3. The overall complication rate was 32.2%, with the most common complications being surgical-site infection, hardware-related complications and delayed wound healing. CONCLUSIONS: PCD is a powerful technique in the management of syndromic craniosynostosis, although complication rates are significantly higher than traditional remodeling techniques. Future studies should compare the effects of supratorcular and infratorcular osteotomies on intracranial volume, cosmesis and complications.

Current state and future direction of quality improvement in pediatric neurosurgery: a survey of pediatric neurosurgeons.

OBJECTIVE: Quality improvement (QI) is a methodology used to implement sustainable, meaningful change to improve patient outcomes. Given the complex pathologies observed in pediatric neurosurgery, QI projects could potentially improve patient care. Overall, there is a need to characterize the degree of QI opportunities, training, and initiatives within the field of pediatric neurosurgery. Herein the authors aimed to define the current QI landscape in pediatric neurosurgery. METHODS: A cross-sectional survey was sent to all members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section on Pediatric Neurological Surgery via email. The responses were anonymized. Questions addressed several relatable QI topics including 1) training and participation in QI; 2) QI infrastructure; 3) QI program incentives; and 4) general opinions on the National Surgical Quality Improvement Program (NSQIP) database, various QI topics, and QI productivity. RESULTS: Responses were received from 129 participants (20% response rate). Most respondents practiced in an academic setting (59.8%) and at a free-standing pediatric hospital (65.4%). Participation in QI projects was high (81.7%), but only 23.8% of respondents had formal QI training. Only 36.5% of respondents had institutional requirements for QI work; the majority of those were only required to participate as a project team member. Nearly half of the respondents did not receive incentives or institutional support for QI. The majority agreed ("strongly" and "somewhat") that a QI course would be beneficial (75.5%), that QI projects should be considered for publication in neurosurgery journals (88.1%), and that there is a need for national quality metrics (81.4%). Over 88% have an interest in seeing QI project presentations at the annual Pediatric Joint Section meeting. Only 26.3% believed that the NSQIP was a useful QI guide. Respondents suggested further study of the following QI topics: overall rates of infection and their prevention, hydrocephalus, standardized treatment algorithms for common disorders, team communication, pediatric neurosurgery-specific database, access to care, and interprofessional education. CONCLUSIONS: Areas of opportunity include specialty-specific QI education, tactics for obtaining support to build the QI infrastructure, increased visibility of QI work within pediatric neurosurgery, and a review of available registries to provide readily available data relevant to this specialty.

Association between synthetic sealants and increased complication rates in posterior fossa decompression with duraplasty for Chiari malformations regardless of graft type.

OBJECTIVE: Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts. METHODS: The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence. RESULTS: From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel. CONCLUSIONS: At the authors' single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.

Diagnosis and Surgical Management of Neonatal Hydrocephalus.

Neonatal hydrocephalus represents an important pathological condition with significant impact on medical care and neurocognitive development. This condition requires early recognition, appropriate medical and surgical management, and long-term surveillance by clinicians and pediatric neurosurgeons. Common etiologies of neonatal and infant hydrocephalus include intraventricular hemorrhage related to prematurity with subsequent post-hemorrhagic hydrocephalus, myelomeningocele, and obstructive hydrocephalus due to aqueductal stenosis. Clinical markers of elevated intracranial pressure include rapid increases in head circumference across percentiles, elevation and firmness of the anterior fontanelle, splitting or splaying of cranial sutures, upgaze palsy, lethargy, frequent emesis, or episodic bradycardia (unrelated to other comorbidities). Complementing these clinical markers, imaging modalities used for the diagnosis of neonatal hydrocephalus include head ultrasonography, brain magnetic resonance imaging, and head computed tomography in urgent or emergent situations. Following diagnosis, temporizing measures may be employed prior to definitive treatment and include ventricular access device or ventriculo-subgaleal shunt insertion. Definitive surgical management involves permanent cerebrospinal fluid (CSF) diversion via CSF shunt insertion, or endoscopic third ventriculostomy with or without choroid plexus cauterization. Surgical decision-making and approaches vary based on patient age, hydrocephalus etiology, neuroanatomy, imaging findings, and medical comorbidities. Indications, surgical techniques, and clinical outcomes of these procedures continue to evolve and elicit significant attention in the research environment. In this review we describe the epidemiology, pathophysiology, clinical markers, imaging findings, early management, definitive surgical management, and clinical outcomes of pediatric patients with neonatal hydrocephalus.

Hospital Case-Volume and Patient Outcomes Following Pediatric Brain Tumor Surgery in the Pediatric Health Information System.

BACKGROUND: Markers of quality of care in various surgical specialties have been shown to correlate with hospital volumes. This study investigates the effect of hospital volume and patient-related factors on the outcomes of children undergoing brain tumor resection. METHODS: We examined the data within the Pediatric Health Information System (PHIS) for children aged zero to 17 years undergoing brain tumor resection between 2016 and 2020. Length of hospital stay (LOS), costs, and reoperation rates were analyzed for associations with hospital case-volume, patient factors, and other hospital-related factors. RESULTS: A total of 2568 patients were included in this PHIS analysis. After adjusting for covariates, care provided by high-case-volume hospitals led to shorter LOS (P = 0.01). The effect of hospital case-volume on median cost was present on univariate analysis (US $63,845 at low-volume hospital versus US $54,909 at high-volume hospital, P = 0.002); this finding was attenuated by LOS. A trend was observed between reoperation rates and hospital case-volume, with lowest quartile volume hospitals having higher odds of reoperation than hospitals with volumes in the highest quartile (P = 0.06). Racial and ethnic minorities, medical comorbidities, and other sociodemographic factors were associated with poorer outcomes following surgery. CONCLUSIONS: Centering care around high-case-volume hospitals can potentially lead to shorter hospital stays and decreased costs for children with brain tumors. This PHIS article highlights the association of the studied outcomes with certain sociodemographic factors and illustrates that inequalities in pediatric health care still exist. Further efforts are required to understand and eliminate these potentially harmful differences.

Comparison of Perioperative Outcomes and Parental Satisfaction Outcomes of Strip Craniectomy with Postoperative Helmet versus Spring-Mediated Remodeling in Sagittal Craniosynostosis.

INTRODUCTION: We sought to compare outcomes and parental satisfaction between 2 approaches for sagittal craniosynostosis: strip craniectomy with spring-mediated skull remodeling (SMSR) and strip craniectomy with postoperative helmet (SCH). METHODS: Perioperative and outcome data for SMSR or SCH patients between September 2010 and July 2019 were retrospectively reviewed. A telephone survey was administered to parents of children who underwent both procedures. RESULTS: A total of 62 children were treated for sagittal craniosynostosis by either SMSR (n = 45) or SCH (n = 17). The SCH group had a lower estimated blood loss (27 vs. 47.06 mL, p = 0.021) and age at surgery (13.0 vs. 19.8 weeks) than the SMSR group. Three patients underwent early springs removal due to trauma or dislodgement, all of whom converted to helmeting. Of the 62 children initially identified, 59 were determined to have an adequate follow-up time to assess long-term outcomes. The mean follow-up time was 30.1 months (n = 16) in the SCH group and 32.0 months in the SMSR group (n = 43, p = 0.39). Two patients in the SCH group and one in the SMSR group converted to open cranial vault reconstruction. Thirty parents agreed to respond to the satisfaction survey (8 SCH, 22 SMSR) based on a Likert scale of responses (0 being most dissatisfied possible, 4 most satisfied possible). Average satisfaction was 3.86/4.0 in the SCH group and 3.45/4.0 in the SMSR group. No parents in the SCH group would change to SMSR, while 3 of the 22 SMSR survey responders would have changed to SCH. CONCLUSIONS: Perioperative outcomes and average parental satisfaction were similar in both groups. Importance of helmet wear compliance and risk of spring dislodgement should be discussed with parents.

Case Series of Rapid Surgical Interventions in Fulminant Intracranial Hypertension.

AIMS: Examine ophthalmologic outcomes and complications of lumbar drain and cerebrospinal fluid shunts in pediatric fulminant intracranial hypertension. METHODS: Patients under 21 years of age with a diagnosis of fulminant intracranial hypertension with temporary lumbar drain only, shunt after lumbar drain, and shunt only were included. Parameters investigated include lumbar drain data, medication freedom, time to resolution of papilledema, improvement in cranial nerve palsy, afferent pupillary defects, visual fields, visual acuity, and complications of each intervention. RESULTS: Four patients had temporary lumbar drain, 2 temporary lumbar drain and cerebrospinal fluid shunt, and 3 shunt only. All achieved medication freedom and resolution of papilledema and cranial nerve palsies (if present). Most had resolution of preprocedure afferent pupillary defects. Minor residual visual field deficits occurred in 67%, and all had visual acuity improvement. One patient's lumbar drain dislodged, and one patient had 2 cerebrospinal fluid shunt revisions. CONCLUSION: Temporary lumbar drain with medical therapy may be a viable first approach to fulminant intracranial hypertension.

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma.

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.

A Case Series of the Use of Piezosurgery Instrument for Minimally Invasive Metopic Suturectomy.

BACKGROUND: Minimal invasive suturectomy is one of the many surgical approaches to treat isolated single suture craniosynostosis. This approach can be technically challenging in metopic craniosynostosis given the narrow corridor and steep angle of the forehead. New instruments such as the Piezosurgery device (Mectron) have the potential to improve the ability to safely perform minimal invasive surgery in metopic craniosynostosis. OBJECTIVE: To demonstrate the safety and efficacy of Piezosurgery technology in minimal invasive suturectomy for nonsyndromic metopic suture craniosynostosis and to describe our technique. METHODS: A retrospective chart review was performed of all the single metopic suturectomies performed at our single institution from March 2018 to November 2019. Pre-, intra-, and postoperative data were collected to assess the safety of Piezosurgery. RESULTS: The cohort consisted of 12 patients with an average of 95.25 d old and an average weight of 6.2 kg. A total of 91.7% were male, and 91.7% were Caucasian. There were no intraoperative or postoperative Piezosurgery device-related complications in the entire cohort. CONCLUSION: The use of the Piezosurgery instrument was safe in this cohort of minimal invasive metopic suturectomy. This device has greatly increased the ease of this procedure in our hands.

Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images.

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.

Spring Cranioplasty: Incorporation Into Practice.

OBJECTIVE: The aim of this paper is to discuss ways to incorporate spring-assisted cranioplasty into the surgical armamentarium for craniosynostosis. BACKGROUND: Spring-assisted cranioplasty after cranial suturectomy for craniosynostosis was popularized in the literature by Dr Lauritzen in 2008 after reporting the results of the first 100 cases. Since that time, more craniofacial surgeons and neurological surgeons have incorporated this surgical technique for treatment of patients presenting with craniosynostosis. This paper will discuss how the team at Nationwide Children's Hospital has incorporated spring-assisted cranioplasty into the care of patients presenting with sagittal synostosis. METHODS: In this article, the authors review our previous protocol for the treatment of children with sagittal synostosis prior to the introduction of spring cranioplasty. The authors then describe the impetus for incorporating spring-assisted cranioplasty for sagittal synostosis into our practice, and barriers we encountered during this implementation. The authors then discuss their current, comprehensive protocol for treating children with sagittal craniosynostosis. Finally, the authors review the expected and unexpected advantages that our craniofacial program has experienced as they implemented spring-assisted cranioplasty. CONCLUSION: Incorporation of spring-assisted cranioplasty for sagittal synostosis offers an additional minimally invasive technique, which presents great advantages for many families, and is rewarding for both craniofacial and neurological surgeons.

Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets.

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.

Pediatric craniopharyngioma.

BACKGROUND: Craniopharyngioma has historically been recognized to be a formidable pathology primarily due to its proximity to critical neurovascular structures and the challenging surgical corridors that surgeons have tried to reach this lesion. FOCUS OF REVIEW: In this work, we review the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to craniopharyngiomas. The management of craniopharyngiomas requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver the most comprehensive and safest surgical resection with minimal postoperative morbidity.

Pediatric pituitary adenomas.

BACKGROUND: Pediatric pituitary adenomas are a rare medical entity that makes up a small portion of intracranial tumors in children and adolescents. Although benign, the majority of these lesions are secreting functional tumors with the potential for physiological sequela that can profoundly affect a child's development. FOCUS OF REVIEW: In this review, we discuss the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to treat these tumors. The management of pituitary tumors requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver comprehensive care.

Management of hydrocephalus in infants with severe hemophilia A: report of 2 cases.

The authors report on the clinical course of two infants with severe hemophilia A (HA) and concomitant progressive hydrocephalus that required management with a ventriculoperitoneal shunt. The first child, with known HA, presented with a spontaneous intracranial hemorrhage and acquired hydrocephalus. He underwent cerebrospinal fluid diversion with a temporary external ventricular drain, followed by placement of a ventriculoperitoneal shunt. The second child had hydrocephalus secondary to a Dandy-Walker malformation and was diagnosed with severe HA during preoperative evaluation. He underwent placement of a ventriculoperitoneal shunt after progression of the hydrocephalus. The authors also review the treatment of hydrocephalus in patients with HA and describe the perioperative protocols used in their two cases. Treatment of hydrocephalus in infants with HA requires unique perioperative management to avoid complications.

Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous.

Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in survival. Faced with dismal survival, great efforts are deployed to find interesting treatment alternatives. However, the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) remain great obstacles to significant drug delivery to brain tumors. The need to optimize delivery strategies for better patient outcome in the treatment of malignant brain tumors is well acknowledged. Certain interesting strategies use surgical or physical techniques to enhance the distribution of therapeutic agents to the central nervous system. The following strategies will be discussed in this review: intra-arterial delivery, osmotic BBB disruption, intranasal delivery, convection-enhanced delivery and osmotic pumps, implanted polymers, magnetic microspheres and ultrasound BBB disruption. The purpose of this paper is to review the importance of the BBB and the BTB and to review the current status and future perspectives of these delivery procedures.