H3K27-altered diffuse midline gliomas with MAPK pathway alterations: Prognostic and therapeutic implications.

Large-scale sequencing led to the identification of driver molecular alterations such as FGFR1 and BRAF in occasional diffuse midline gliomas (DMGs) H3K27-mutant but their significance has not been completely explored. We evaluated these associations in our institutional cohorts. We searched our archives for H3K2M7-mutant gliomas and analyzed the co-occurring genetic alterations. The demographics, clinical information, and pathology were reviewed. Oncoplots and Kaplan-Meier survival curves were generated with the maftools R package. We identified 81 patients (age range 2-68, median 26), of which 79 (97%) were DMGs, and 2 were glioneuronal tumors. The 2 glioneuronal tumors (1 with BRAF fusion and 1 BRAF-V600E-mutant) were removed from the outcome analysis. Four cases had BRAF V600E mutation, 12 had FGFR1 hotspot mutations, and one each had KRAS and NRAS pathogenic mutations. The most common correlating anatomic location was the brainstem for the BRAF group and thalamus for the FGFR1group. Follow-up ranged from 0 to 78 months, average 20.4 months. The overall survival in FGFR1- and BRAF V600E-mutant DMGs was not statistically improved when compared with those that were wildtype. However, the possibility of targeted therapy argues for comprehensive sequencing of H3K27-altered gliomas.

Endoscopic third ventriculostomy with choroid plexus cauterization: predictors of long-term success and comparison with shunt placement for primary treatment of infant hydrocephalus.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) can avoid ventriculoperitoneal shunt (VPS) dependence in very young hydrocephalic children, although long-term success as a primary treatment in North America has not been previously reported. Moreover, optimal age at surgery, impact of preoperative ventriculomegaly, and relationship to prior cerebrospinal fluid (CSF) diversion remain poorly defined. The authors compared ETV/CPC and VPS placement for averting reoperation, and they evaluated preoperative predictors for reoperation and shunt placement after ETV/CPC. METHODS: All patients under 12 months of age who underwent initial hydrocephalus treatment via ETV/CPC or VPS placement at Boston Children's Hospital between December 2008 and August 2021 were reviewed. Analyses included Cox regression for independent outcome predictors, and both Kaplan-Meier and log-rank rank tests for time-to-event outcomes. Cutoff values for age and preoperative frontal and occipital horn ratio (FOHR) were determined with receiver operating characteristic curve analysis and Youden's J index. RESULTS: In total, 348 children (150 females) were included with principal etiologies of posthemorrhagic hydrocephalus (26.7%), myelomeningocele (20.1%), and aqueduct stenosis (17.0%). Of these, 266 (76.4%) underwent ETV/CPC and 82 (23.6%) underwent VPS placement. Treatment choice largely reflected surgeon preferences before practice shifted toward endoscopy, with endoscopy not considered for > 70% of initial VPS cases. ETV/CPC patients trended toward fewer reoperations, and Kaplan-Meier analysis estimated that 59% of patients would achieve long-term shunt freedom through 11 years (median 42 months of actual follow-up). Among all patients, corrected age < 2.5 months (p < 0.001), prior temporizing CSF diversion (p = 0.003), and excess intraoperative bleeding (p < 0.001) independently predicted reoperation. Among ETV/CPC patients, corrected age < 2.5 months (p = 0.031), prior CSF diversion (p = 0.001), preoperative FOHR > 0.613 (p = 0.011), and excessive intraoperative bleeding (p = 0.001) independently predicted ultimate conversion to VPS. The actual VPS insertion rates remained low in patients who were ≥ 2.5 months old at ETV/CPC either with prior CSF diversion (2/10 [20.0%]) or without prior CSF diversion (24/123 [19.5%]); however, the actual VPS insertion rates increased in patients who were < 2.5 months old at ETV/CPC with prior CSF diversion (19/26 [73.1%]) or without prior CSF diversion (44/107 [41.1%]). CONCLUSIONS: ETV/CPC successfully treated hydrocephalus in most patients younger than 1 year irrespective of etiology, averting observed shunt dependence in 80% of patients ≥ 2.5 months of age regardless of prior CSF diversion and in 59% of those < 2.5 months of age without prior CSF diversion. For infants aged < 2.5 months with prior CSF diversion, particularly those with severe ventriculomegaly, ETV/CPC was unlikely to succeed unless safely delayed.

Machine Learning in the Classification of Pediatric Posterior Fossa Tumors: A Systematic Review.

Background: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive appropriate treatment, definitive diagnosis is currently only achievable through invasive tissue collection and histopathological analyses. Machine learning has been investigated as an alternative means of diagnosis. In this systematic review and meta-analysis, we evaluated the primary literature to identify all machine learning algorithms developed to classify and diagnose pediatric PFTs using imaging or molecular data. Methods: Of the 433 primary papers identified in PubMed, EMBASE, and Web of Science, 25 ultimately met the inclusion criteria. The included papers were extracted for algorithm architecture, study parameters, performance, strengths, and limitations. Results: The algorithms exhibited variable performance based on sample size, classifier(s) used, and individual tumor types being investigated. Ependymoma, medulloblastoma, and pilocytic astrocytoma were the most studied tumors with algorithm accuracies ranging from 37.5% to 94.5%. A minority of studies compared the developed algorithm to a trained neuroradiologist, with three imaging-based algorithms yielding superior performance. Common algorithm and study limitations included small sample sizes, uneven representation of individual tumor types, inconsistent performance reporting, and a lack of application in the clinical environment. Conclusions: Artificial intelligence has the potential to improve the speed and accuracy of diagnosis in this field if the right algorithm is applied to the right scenario. Work is needed to standardize outcome reporting and facilitate additional trials to allow for clinical uptake.

Optic nerve compression in craniopharyngioma by taut anterior cerebral arteries visualized in frontal and transsphenoidal exposures: illustrative cases.

BACKGROUND: During initial exposure and removal of craniopharyngioma in pediatric patients with severe visual field deficits, the authors have encountered severe deformation of the optic apparatus by taut anterior cerebral arteries as seen during both frontal craniotomy and transsphenoidal exposures. OBSERVATIONS: The authors report two pediatric patients with craniopharyngioma whose severe preoperative visual deficits were associated not only with large suprasellar masses but also with severe optic nerve and chiasm compression by taut anterior cerebral arteries. In each patient, the optic nerves were partially cleft by these vessels' indenting them. LESSONS: The role of a taut anterior cerebral artery complex in compression of the optic apparatus in patients with suprasellar tumors has been reported previously, but the intraoperative images in these two cases dramatically reveal this phenomenon.

Management strategies for recurrent pediatric craniopharyngioma: new recommendations.

OBJECTIVE: The goal of this study was to identify the independent risk factors for recurrence or progression of pediatric craniopharyngioma and to establish predictors of the appropriate timing of intervention and best management strategy in the setting of recurrence/progression, with the aim of optimizing tumor control. METHODS: This is a retrospective cohort study of all pediatric patients with craniopharyngioma who were diagnosed and treated at Boston Children's Hospital between 1990 and 2017. This study was approved by the institutional review board at Boston Children's Hospital. All statistical analyses were performed using Stata software. RESULTS: Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at the time of diagnosis was 8.6 ± 4.4 years (range 1.2-19.7 years). The mean follow-up was 10.9 ± 6.5 years (range 1.3-24.6 years). Overall, 30/80 (37.5%) patients developed recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3-108 months). Subtotal resection with no adjuvant radiotherapy (p < 0.001) and fine calcifications (p = 0.008) are independent risk factors for recurrence/progression. An increase (%) in the maximum dimension of the tumor at the time of recurrence/progression was considered a statistically significant predictor of the appropriate timing of intervention. CONCLUSIONS: Based on the identified independent risk factors for tumor recurrence/progression and the predictors of appropriate timing of intervention in the setting of recurrence/progression, the authors propose an algorithm for optimal management of recurrent pediatric craniopharyngioma to increase the likelihood of tumor control.

Postoperative MR imaging surveillance of pediatric craniopharyngioma: new institutional guidelines.

PURPOSE: To develop postoperative surveillance protocols that yield efficient detection rates of tumor recurrence or progression using fewer imaging studies and less cost. METHOD: This is a retrospective cohort study of all pediatric craniopharyngioma patients who have been diagnosed and treated at Boston Children's Hospital (BCH) between 1990 and 2017. All statistical analyses were performed using Stata. RESULTS: Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at time of diagnosis was 8.6 ± 4.4 years. The mean follow-up period was 10.9 ± 6.5 years. Overall 30/80 (37.5%) patients experienced tumor recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3 to 108 months), with 76.6% of the recurrences/progressions taking place within the first 2 years postoperatively. Given the lack of any clinical symptoms/signs associated with the vast majority of the recurrent/progressed cases, we propose postoperative MR imaging surveillance protocols that are substantially less intensive than the current practice. Therefore, we recommend the following postoperative MR imaging surveillance protocols, stratified by management strategies; 0, 9, 15, 36, 48, and 60 months for patients who underwent GTR, 0, 3, 6,12, 18, and 24 months for patients who underwent STR alone and 0, 3, 12, 72, 96, and 120 months for patients who underwent STR followed by subsequent XRT. CONCLUSION: The proposed postoperative MR imaging surveillance protocols would provide a potential 50% decrement of healthcare costs. It may also minify the psychological burden of frequent MR scanning for these patients and their families.

Measure Twice: Promise of Liquid Biopsy in Pediatric High-Grade Gliomas.

PURPOSE: To review and critique the current state of liquid biopsy in pHGG. MATERIALS AND METHODS: Published literature was reviewed for articles related to liquid biopsy in pediatric glioma and adult glioma with a focus on high-grade gliomas. RESULTS: This review discusses the current state of liquid biomarkers of pHGG and their potential applications for liquid biopsy development. CONCLUSIONS: While nascent, the progress toward identifying circulating analytes of pHGG primes the field of neuro-oncoogy for liquid biopsy development.

Complications following pediatric cranioplasty after decompressive craniectomy: a multicenter retrospective study.

OBJECTIVE In children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty. METHODS The authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty. RESULTS A total of 359 patients met the inclusion criteria. The patients' mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17-4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03-5.79), and ventilator dependence (OR 8.45, 95% CI 1.10-65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection. Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98-0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts. CONCLUSIONS This is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.

Incidence of symptomatic tethered spinal cord in pediatric patients presenting with neurofibromatosis types 1 and 2.

OBJECTIVE The relationship between a tethered cord (TC) and neurofibromatosis type 1 (NF1) and NF2 is not known. The purpose of this study was to define the incidence of TC in pediatric neurosurgical patients who present with NF. METHODS The authors performed a single-institution (tertiary care pediatric hospital) 10-year retrospective analysis of patients who were diagnosed with or who underwent surgery for a TC and/or NF. Clinical and radiological characteristics were analyzed, as was histopathology. RESULTS A total of 424 patients underwent surgery for a TC during the study period, and 67 patients with NF were seen in the pediatric neurosurgery clinic. Of these 67 patients, 9 (13%) were diagnosed with a TC, and filum lysis surgery was recommended. Among the 9 patients with NF recommended for TC-release surgery, 4 (44%) were female, the mean age was 8 years (range 4-14 years), the conus position ranged from L1-2 to L-3, and 3 (33%) had a filum lipoma, defined as high signal intensity on T1-weighted MR images. All 9 of these patients presented with neuromotor, skeletal, voiding, and/or pain-related symptoms. Histopathological examination consistently revealed dense fibroconnective tissue and blood vessels. CONCLUSIONS Despite the lack of any known pathophysiological relationship between NF and TC, the incidence of a symptomatic TC in patients with NF1 and NF2 who presented for any reason to this tertiary care pediatric neurosurgery clinic was 13%. Counseling patients and families regarding TC symptomatology might be indicated in this patient population.

Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization.

Vasculopathy is well-described in Alagille syndrome (ALGS); however, few data exist regarding neurosurgical interventions. We report 5 children with ALGS with moyamoya who underwent revascularization surgery. Postsurgical complications included 1 stroke and 1 death from thalamic hemorrhage. Global function improved in survivors. Revascularization is reasonably safe in patients with ALGS and may improve neurologic outcomes.

Spontaneous regression of an epidermoid cyst of the cavernous sinus.

Epidermoid cysts are rare lesions in the pediatric population. The natural history of epidermoids is usually that of slow growth, although rupture and cases of malignant transformation have been reported. Spontaneous regression of an intracranial epidermoid cyst has not previously been described to our knowledge. We present a 3-year-old boy who presented with severe vertigo. MRI was performed which revealed a 2cm non-enhancing lesion in the right cavernous sinus. The lesion was T1-hypoinsense, T2-hyperintense, and with evidence of restricted diffusion, consistent with an epidermoid cyst. The patient was followed with annual MRI studies over the next 3years, demonstrating progressive reduction in the size of the lesion over time, with complete resolution after 3years. The child's symptoms also resolved during this period. Long-term follow-up imaging at 5years showed no evident lesion. To our knowledge, this is the first report documenting spontaneous regression of an intracranial epidermoid cyst. While isolated, this finding demonstrates the potential for involution of epidermoids and lends support to the clinical practice of careful observation of these lesions, especially when located in areas associated with high potential surgical morbidity. Importantly, the novelty of this observation suggests a need for further study to better elucidate the underlying mechanism of this regression.

Third-ventricular neurocysticercosis: hydraulic maneuvers facilitating endoscopic resection.

BACKGROUND: Neurocysticercosis, an infection of the central nervous system with the larval cysts of the pork tapeworm, Taenia solium, is the most common parasitic disease of the central nervous system. The disease is a major global cause of acquired epilepsy and may also manifest as intracranial hypertension due to mass effect from large cysts or to cerebrospinal fluid flow obstruction by intraventricular cysts or inflammation of the subarachnoid space. While the condition is endemic in several regions of the world and has been appreciated as a public health problem in such regions for several decades, its emergence in the USA in areas far from the Mexican border is a more recent phenomenon. METHODS: We present a case of surgically corrected acute hydrocephalus in a recent Haitian emigrant child due to a third ventricular neurocysticercal cyst complex. RESULTS: We describe the endoscope-assisted en bloc removal of the complex, together with hydraulic maneuvers facilitating the removal of the intact cyst. CONCLUSIONS: Simple hydraulic maneuvers can facilitate the endoscopic en bloc removal of third ventricular neurocysticercal cysts.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with hydrocephalus: a systematic review and meta-analysis.

OBJECT: The objective of this systematic review and meta-analysis was twofold: to answer the question "What is the evidence for the effectiveness of prophylactic intravenous antibiotics for infection prevention in shunt surgery?" and to make treatment recommendations based on the available evidence. METHODS: The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to prophylactic antibiotic use in children undergoing a shunt operation. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). A meta-analysis was conducted using a random-effects model to calculate a cumulative estimate of treatment effect using risk ratio (RR). Heterogeneity was assessed using chi-square and I(2) statistics. A sensitivity analysis was also conducted. Based on the quality of the literature and the result of the meta-analysis, a recommendation was rendered (Level I, II, or III). RESULTS: Nine studies (4 Class I, 3 Class II, and 2 Class III) met our inclusion criteria. Of 7 randomized controlled trials (RCTs), 3 were downgraded from Class I to Class II because of significant quality issues, and all RCTs were potentially underpowered. In only 2 Class in retrospective cohort studies were preoperative antibiotic agents found to be protective against shunt infection. When data from the individual studies were pooled together, the infection rate in the prophylactic antibiotics group was 5.9% compared with 10.7% in the control group. Using a random-effects model, the cumulative RR was 0.55 (95% CI 0.38-0.81), indicating a protective benefit of prophylactic preoperative intravenous antibiotics. A sensitivity analysis of RCTs only (n = 7) also demonstrated a statistical benefit, but an analysis of higher-quality RCTs only (n = 4) did not. Conclusions Within the limits of this systematic review and meta-analysis, administration of preoperative antibiotic agents for shunt surgery in children was found to lower the infection risk (quality of evidence: Class II; strength of recommendation, Level II). RECOMMENDATION: The use of preoperative antibiotic agents can be recommended to prevent shunt infection in patients with hydrocephalus. It was only by combining the results of the various underpowered studies (meta-analysis) that the use of preoperative antibiotics for shunt surgery in children was shown to lower the risk of shunt infection. STRENGTH OF RECOMMENDATION: Level II, moderate degree of clinical certainty.

A single spinal lesion arising from an intradural meningioma contiguous with an extradural lymphoma.

The authors describe here a unique case of contiguous, synchronous meningioma and lymphoma in the spinal column. Both tumors were present at the same vertebral level, one intradural and the other extradural. A patient presented with bilateral leg pain, acute weakness, and sensory loss in the lower extremities. Magnetic resonance imaging revealed an intradural mass at T6-7 with ambiguous boundaries relative to the thecal sac and compressing the spinal cord. The patient underwent resection of the epidural and intradural mass at T6-7. Histopathology revealed the epidural specimen to be a double-hit B-cell lymphoma and the intradural mass to be a transitional meningioma. Postoperatively, the patient did well, with an immediate return of strength and sensation. A postoperative MR image showed complete resection of the intradural mass. The authors suggest that biopsy may be prudent in patients with known systemic lymphoma presenting with a spinal lesion that has unclear boundaries relative to the thecal sac prior to commencing radiation and chemotherapy.

Craniofacial reconstruction as a treatment for elevated intracranial pressure.

INTRODUCTION: Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The authors review their institutional experience in the treatment of children with symptomatic increased intracranial pressure (ICP) utilizing craniofacial reconstructive procedures. METHODS: The senior authors' (HSM, SRC) craniofacial experience of 222 patients over a 7-year period from 2000 to 2007 at a single institution (Rady Children's Hospital, San Diego) is reviewed. Seventeen patients were identified who were felt to be candidates for craniofacial surgery with symptomatic increased ICP. RESULTS: Patient diagnoses included single-suture craniosynostosis, craniofacial dysostoses, shunt-induced craniostenosis, and shunt-associated intracranial hypertension (slit-ventricle syndrome). Seventeen patients underwent 21 craniofacial procedures. Age at surgery ranged from 3 months to 13 years with a mean of 5 years. Preoperative symptoms and signs included headaches, unexplained irritability, seizures, papilledema, and visual loss. All patients had diagnostic neuroimaging. Seven patients had preoperative invasive ICP measurements. Surgery was deferred on three of these patients based on these measurements. The mean total operative (including anesthetic preparation) and surgical times were 3 h 12 min and 2 h 20 min, respectively. Percentage operative blood loss averaged 11.3%. In six procedures, no transfusions were required. Average hospital stay was 4 days. There was no perioperative mortality or significant surgery associated morbidity. All patients have had postoperative clinical improvement in signs and symptoms of increased ICP. CONCLUSIONS: Using modern diagnostic and surgical techniques, including invasive ICP monitoring, increased intracranial pressure can be successfully managed by an experienced, multidisciplinary, craniofacial team. Our treatment paradigm and operative management scheme is discussed.

Minimally disruptive decompression and transforaminal lumbar interbody fusion.

BACKGROUND: Posterior spinal procedures through tubular exposures have been described. However, tubes restrain visibility and require co-axial instrument manipulation, increasing difficulty and potentially compromising surgical results. An independent-blade retractor system overcomes the obstacles of working through a tube and has been used to perform minimally-disruptive decompression and instrumented tranforaminal lumbar interbody fusion (TLIF). PURPOSE: To evaluate the advantages to patient recovery and surgical efficacy of this technique. METHODS/RESULTS: Retrospective review of technique employing a minimally-disruptive approach to decompression and transforaminal lumber interbody fusion (TLIF). CONCLUSIONS: Minimally-disruptive decompression and instrumented TLIF can be performed in a safe and effective manner using an independent-blade retractor system. Relative to traditional-open techniques, surgical goals can be accomplished, but with the benefits of minimally-disruptive surgery.