Treatment of hydrocephalus following fetal repair of myelomeningocele: comparing endoscopic third ventriculostomy with choroid plexus cauterization to ventricular shunting.

OBJECTIVE: The aim of this study was to compare clinical and craniometric outcomes of patients treated for hydrocephalus following fetal myelomeningocele repair (fMMR) via a ventriculoperitoneal shunt (VPS) or endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC). METHODS: This was a retrospective cohort study of children who were treated for hydrocephalus following fMMR via VPS or ETV with or without CPC (ETV ± CPC) at Vanderbilt between 2012 and 2021. The primary outcomes were treatment failure and time to failure (TTF). Secondary outcomes included changes in hydrocephalus metrics (fronto-occipital horn ratio [FOHR] and head circumference measurements) and healthcare resource utilization (number of hospital admissions, clinic visits, and neuroimaging findings). RESULTS: Among 88 patients who underwent fMMR, 37 (42%) required permanent CSF diversion, of whom 19 received treatment at the authors' institution. Twelve patients underwent ETV ± CPC, and 7 underwent VPS placement at a median corrected age of 23 weeks versus 1 week (p = 0.002). The preoperative median head circumference percentiles and z-scores for patients in the ETV ± CPC cohort were similar to those of the VPS cohort (percentiles: 98.5 vs 94.0, p = 0.064; z-scores: 2.32 vs 1.60, p = 0.111). There was no difference in preoperative median FOHR measurements between the two cohorts (0.57 vs 0.59, p = 0.53). At 6 months postoperatively, the median head circumference percentile and z-score for the ETV ± CPC cohort remained similar between the two cohorts (percentiles: 98.0 vs 67.5, p = 0.315; z-scores: 2.12 vs 0.52, p = 0.307). There was no difference in the change in FOHR (-0.06 vs -0.09, p = 0.37) and change in head circumference percentile (-1.33 vs -28.6, p = 0.058) between the cohorts 6 months after the index CSF diversion procedure. One patient in the ETV ± CPC cohort experienced a seizure and a nonoperative subdural hemorrhage postoperatively; no other complications were observed. Six of the 7 patients in the VPS cohort required shunt revision with a median TTF of 9.8 months while 2 of the 12 ETV ± CPC patients required a repeat ETV at a median of 17.5 months (86% vs 17%, p = 0.013). The median number of hydrocephalus-related hospital readmissions was significantly lower in the ETV ± CPC cohort than in the VPS cohort (0 vs 1, p = 0.006). The ETV ± CPC cohort had fewer CT scans (0 vs 2, p = 0.004) and radiographs (0 vs 2, p < 0.001) than the VPS cohort. CONCLUSIONS: In a single-center cohort, hydrocephalic fMMR patients treated via ETV ± CPC remained shunt free, while a majority of patients receiving an upfront shunt required revision. This is the first study comparing ETV ± CPC with VPS in the fMMR hydrocephalus population. While larger, multicenter studies are needed, these results suggest that ETV/CPC may be a preferred means of CSF diversion following fMMR.

Sub-Saharan African experience of neurosurgical oncology care: challenges and barriers encountered at 7 cancer treatment centers.

OBJECTIVE: Wide disparities in neurosurgical oncology care and treatment outcomes exist globally despite recent improvements in diagnostics and cancer therapy. To better understand the challenges to neurosurgical oncology care in low-resource settings, the authors collected data on national neurosurgical capacity and hospital diagnostic and treatment capacity across 7 national referral hospitals in 7 countries in sub-Saharan Africa (SSA). METHODS: In April 2023, a 42-item self-administered questionnaire was distributed to partner neurosurgeons at the 7 centers via REDCap to provide country- and hospital-level capacity data on neurosurgical oncology care. RESULTS: Neurosurgical and neurosurgical oncology care were reported to be available in a limited number of provinces, states, regions, and counties in 6 of the 7 countries. The general neurosurgical workforce density across the 7 countries ranged from 0.03 to 0.67 per 100,000 persons, and that of the pediatric neurosurgical workforce ranged from 0 to 0.05 per 100,000 persons. Two centers had no pediatric ICUs, and the remaining 5 centers had pediatric ICUs with bed capacities between 1 and 8. One hospital had neither a CT nor an MRI scanner available and relied solely on private diagnostic facilities for neuroimaging. Histopathology services were largely limited to basic histopathology staining only; molecular subtyping was available at a single center. Three hospitals offered pediatric anesthesia expertise. None of the hospitals offered subspecialty neuro-oncology care or had a pediatric neuro-oncologist. None of the 7 hospitals had formal neurocritical care, neuroradiology, or neuropathology expertise. Neither adjuvant chemotherapy nor radiotherapy was available at 3 centers. Rehabilitation was largely limited to basic physical and occupational therapy at all 7 centers. Although all 7 countries had a multiple health payer system, the payment structure differed across the 7 hospitals for different neurosurgical oncology services, with patients making out-of-pocket payments for all services in some cases. CONCLUSIONS: There are significant challenges to timely and quality neurosurgical oncology care in SSA especially for children. System-level interventions are needed to strengthen neurosurgical oncology care capacity in SSA.

Understanding diffuse leptomeningeal glioneuronal tumors.

INTODUCTION: Diffuse leptomeningeal glioneuronal tumors (DLGNTs) pose a rare and challenging entity within pediatric central nervous system neoplasms. Despite their rarity, DLGNTs exhibit complex clinical presentations and unique molecular characteristics, necessitating a deeper understanding of their diagnostic and therapeutic nuances. METHODS: This review synthesizes contemporary literature on DLGNT, encompassing epidemiology, clinical manifestations, pathological features, treatment strategies, prognostic markers, and future research directions. To compile the existing body of knowledge on DLGNT, a comprehensive search of relevant databases was conducted. RESULTS: DLGNT primarily affects pediatric populations but can manifest across all age groups. Its diagnosis is confounded by nonspecific clinical presentations and overlapping radiological features with other CNS neoplasms. Magnetic resonance imaging (MRI) serves as a cornerstone for DLGNT diagnosis, revealing characteristic leptomeningeal enhancement and intraparenchymal involvement. Histologically, DLGNT presents with low to moderate cellularity and exhibits molecular alterations in the MAPK/ERK signalling pathway. Optimal management of DLGNT necessitates a multidisciplinary approach encompassing surgical resection, chemotherapy, radiotherapy, and emerging targeted therapies directed against specific genetic alterations. Prognostication remains challenging, with factors such as age at diagnosis, histological subtypes, and genetic alterations influencing disease progression and treatment response. Long-term survival data are limited, underscoring the need for collaborative research efforts. CONCLUSION: Advancements in molecular profiling, targeted therapies, and international collaborations hold promise for improving DLGNT outcomes. Harnessing the collective expertise of clinicians, researchers, and patient advocates, can advance the field of DLGNT research and optimize patient care paradigms.

The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact.

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Complications associated with combined direct and indirect bypass in Moyamoya Disease: A meta-analysis.

Bypass revascularization helps prevent complications in Moyamoya Disease (MMD). To systematically review complications associated with combined direct and indirect (CB) bypass in MMD and analyze differences between the adult and pediatric populations. A systematic literature review was conducted per PRISMA guidelines. PUBMED, Cochrane Library, Web of Science, and CINAHL, were queried from January 1980 to March 2022. Complications were defined as any event in the immediate post-surgical period of a minimum 3 months follow-up. Exclusion criteria included lack of surgical complication reports, non-English articles, and CB unspecified or reported separately. 18 final studies were included of 1580 procured. 1151 patients (per study range = 10-150, mean = 63.9) were analyzed. 9 (50.0%) studies included pediatric patients. There were 32 total hemorrhagic, 74 total ischemic and 16 total seizure complications, resulting in a rate of 0.04 (95% CI 0.03, 0.06), 0.7 (95% CI 0.04, 0.10) and 0.03 (95% CI 0.02, 0.05), respectively. The rate of hemorrhagic complications in the pediatric showed no significant difference from the adult subgroup (0.03 (95% CI 0.01-0.08) vs. 0.06 (95% CI 0.04-0.10, p = 0.19), such as the rate of ischemic complications (0.12 (95% CI 0.07-0.23) vs. 0.09 (95% CI 0.05-0.14, p = 0.40). Ischemia is the most common complication in CB for MMD. Pediatric patients had similar hemorrhagic and ischemic complication rates compared to adults.

Complications following resection of primary and recurrent pediatric posterior fossa ependymoma.

OBJECTIVE: Extent of resection (EOR) is the most important modifiable prognostic variable for pediatric patients with posterior fossa ependymoma. An understanding of primary and recurrent ependymoma complications is essential to inform clinical decision-making for providers, patients, and families. In this study, the authors characterize postsurgical complications following resection of primary and recurrent pediatric posterior fossa ependymoma in a molecularly defined cohort. METHODS: The authors conducted a 20-year retrospective single-center review of pediatric patients undergoing resection of posterior fossa ependymoma at the Hospital for Sick Children in Toronto, Canada. Complications were dichotomized into major and minor groups; EOR was compared across complication categories. The association between complication occurrence with length of stay (LOS) and mortality was also assessed using multivariable regressions. RESULTS: There were 60 patients with primary resection included, 41 (68%) of whom were alive at the time of data collection. Gross-total resection was achieved in 33 (58%) of 57 patients at primary resection. There were no 30-day mortality events following primary and recurrent ependymoma resection. Following primary resection, 6 patients (10%) had posterior fossa syndrome (PFS) and 36 (60%) developed cranial neuropathies, 56% of which recovered within 1 year. One patient (1.7%) required a tracheostomy and 9 patients (15%) required gastrostomy tubes. There were 14 ventriculoperitoneal shunts (23%) inserted for postoperative hydrocephalus. Among recurrent cases, there were 48 recurrent resections performed in 24 patients. Complications included new cranial neuropathy in 10 patients (21%), of which 5 neuropathies resolved within 1 year. There were no cases of PFS following resection of recurrent ependymoma. Gastrostomy tube insertion was required in 3 patients (6.3%), and 1 patient (2.0%) required a tracheostomy. Given the differences in the location of tumor recurrence, a direct comparison between primary and recurrent resection complications was not feasible. Following multivariate analysis adjusting for sex, age, molecular status, and EOR, occurrence of major complications was found to be associated with prolonged LOS but not mortality. CONCLUSIONS: These results detail the spectrum of postsurgical morbidity following primary and recurrent posterior fossa ependymoma resection. The crude complication rate following resection of infratentorial recurrent ependymoma was lower than that of primary ependymoma, although a statistical comparison revealed no significant differences between the groups. These results should serve to inform providers of the morbidity profile following surgical management of posterior fossa ependymoma and inform perioperative counseling of patients and their families.

Global pediatric craniopharyngioma management modalities and outcomes.

INTRODUCTION: Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies have compared various treatment modalities and outcomes described in different global regions. We conducted a comprehensive systematic review to compare demographics, clinical presentation, treatment approach and outcomes of children diagnosed with craniopharyngioma globally. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "craniopharyngioma" and country-specific terms. Inclusion criteria included full-text studies published between 2000-2022, primarily examining pediatric patients 18-years old or younger diagnosed with craniopharyngioma, and reporting management and outcomes of interest. Data extracted included country of origin, demographical data, initial presentation and treatment modality, and outcomes. Descriptive statistics and between-group comparisons based on country of origin were performed. RESULTS: Of 797 search results, 35 articles were included, mostly originating from high-income countries (HIC) (n = 25, 71.4%). No studies originated from low-income countries (LIC). When comparing HIC to middle-income countries (MIC), no differences in patient demographics were observed. No differences in symptomatology at initial presentation, tumor type, surgical approach or extent of surgical resection were observed. HIC patients undergoing intracystic therapy were more likely to receive bleomycin (n = 48, 85.7%), while the majority of MIC patients received interferon therapy (n = 10, 62.5%). All MIC patients undergoing radiation therapy underwent photon therapy (n = 102). No statistically significant differences were observed in postoperative complications or mean follow-up duration between HIC and MIC (78.1 ± 32.2 vs. 58.5 ± 32.1 months, p = 0.241). CONCLUSION: Pediatric craniopharyngioma presents and is managed similarly across the globe. However, no studies originating from LICs and resource-poor regions examine presentation and management to date, representing a significant knowledge gap that must be addressed to complete the global picture of pediatric craniopharyngioma burden and management.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Postoperative cerebellar mutism syndrome is an acquired Autism-like network disturbance.

BACKGROUND: Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumour surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates. METHODS: In this study, we analyzed post-operative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and paediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n=427). RESULTS: Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the paediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviours. CONCLUSIONS: Our findings indicate that CMS-associated lesions result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children.

Pediatric neurosurgical-oncology scope and management paradigms in Sub-Saharan Africa: a collaboration among 7 referral hospitals on the subcontinent.

Background: Understanding of the epidemiology and biology of pediatric CNS tumors has advanced dramatically over the last decade; however there remains a discrepancy in the understanding of epidemiologic data and clinical capacity between high- and lower-income countries. Objective: We collected and analyzed hospital-level burden and capacity-oriented data from pediatric neurosurgical oncology units at 7 referral hospitals in Sub-Saharan Africa (SSA). Methods: A cross sectional epidemiological survey was conducted using REDCap at the 7 SSA sites, capturing 3-month aggregate data for patients managed over a total of 9 months. Descriptive statistical analyses for the aggregate data were performed. Results: Across the neurosurgical spectrum, 15% of neurosurgery outpatient and 16% of neurosurgery operative volume was represented by pediatric neuro-oncology across the 7 study sites. Eighty-six percent and 87% of patients who received surgery underwent preoperative CT scan and/or MRI respectively. Among 312 patients evaluated with a CNS tumor, 211 (68%) underwent surgery. Mean surgery wait time was 26.6 ± 36.3 days after initial presentation at the clinic. The most common tumor location was posterior fossa (n=94, 30%), followed by sellar/suprasellar region (n=56, 18%). Histopathologic analysis was performed for 189 patients (89%). The most common pathologic diagnosis was low grade glioma (n=43, 23%), followed by medulloblastoma (n=37, 20%), and craniopharyngioma (n=31, 17%). Among patients for whom adjuvant therapy was indicated, only 26% received chemotherapy and 15% received radiotherapy. Conclusion: The histopathologic variety of pediatric brain and spinal tumors managed across 7 SSA referral hospitals was similar to published accounts from other parts of the world. About two-thirds of patients received a tumor-directed surgery with significant inter-institutional variability. Less than a third of patients received adjuvant therapy when indicated. Multi-dimensional capacity building efforts in neuro-oncology are necessary to approach parity in the management of children with brain and spinal tumors in SSA.

Geographical Distribution of Neurosurgeons and Emergency Neurosurgical Services in Pakistan.

BACKGROUND AND OBJECTIVE: According to the World Federation of Neurosurgical Societies (WFNS), a minimum neurosurgery workforce density should be 1 per 200,000 population for optimum access to neurosurgical care. Pakistan lags behind in the number of neurosurgeons, and disproportionate geographical distribution further increases disparity. Our objective was to geographically map the density of neurosurgeons and emergency neurosurgical services (ENS) in Pakistan. METHODS: This survey was circulated among 307 neurosurgeons. Data were analyzed using SPSS v21. The number of neurosurgeons and ENS were plotted on the population density map using ArcGIS Pro 3.0.0 software. RESULTS: Three hundred and seven neurosurgeons working at 74 centers responded to our survey (93.3% coverage). The current density of neurosurgeons in Pakistan is 0.14/100,000. The 2 more populous provinces, Punjab and Sindh, have 42.3% (130) and 35.8% (110) neurosurgeons, respectively. They also housed nearly 3 quarters of all the neurosurgery centers in urban districts. Karachi and Lahore accommodate 135 (44%) of all the country's neurosurgeons, having 0.29 and 0.51 neurosurgeons/100,000 respectively. Management of traumatic brain injury is offered at 65 centers (87.8%). Nearly all centers are equipped with computed tomography (CT) scan machine (74; 97%), but magnetic resonance imaging (MRI) facility is available at 55 (72%) centers and 37 (49%) centers have angiography suites. Sixty nine centers (93.2%) have C-arm fluoroscopes available. CONCLUSIONS: The geographical mapping of neurosurgeons and neurosurgical facilities is highly skewed towards urban centers, increasing disparity in access to timely neurosurgical emergency services. Four times more neurosurgeons are required in Pakistan to bridge the gap in neurosurgical workforce.

Current State of Brazilian Neurosurgery: Evaluation of Burden of Care and Case Volume.

BACKGROUND: Low- and middle-income countries (LMICs) bear a heavier burden of neurosurgical diseases than high-income countries. Brazil, a growing middle-income country, holds promise as a health care market. However, there exists a lack of information to characterize the state of neurosurgical practice and access to care in Brazil. This study aimed to characterize neurosurgical practice in Brazil and identify barriers to care. METHODS: A collaborative survey was developed with Brazilian neurosurgeons and distributed by the Brazilian Society of Neurosurgery. The survey gathered demographic information, practice characteristics, case volume, referral patterns, income sources, and assessed barriers using a Likert scale. Descriptive statistics were employed for data analysis. RESULTS: One-hundred and forty-nine neurosurgeons participated (response rate: 17.5%), representing various states in Brazil. Neurosurgeons practiced in more than 4 different hospital systems on average, with most consultations and procedures occurring in public hospitals. Common procedures included tumor surgeries, general neurosurgery, spine surgeries, trauma surgeries, and hydrocephalus management. Equipment shortage and systemic issues were identified as major barriers to care. CONCLUSIONS: Neurosurgical practice in Brazil exhibits diverse age distribution, widespread distribution across states, and involvement in both public and private hospitals. Survey insights shed light on neurosurgical workload and neurosurgical practice characterization. Lack of equipment and inadequate postoperative resources pose significant barriers to care. The findings highlight the need for investments in equipment, critical care facilities, and improved health care system coordination to enhance access to neurosurgical care in Brazil.

Recurrent TRAK1::RAF1 Fusions in pediatric low-grade gliomas.

Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low-grade glial-glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5' of the kinase domain, while the breakpoints in the 3' partner preserved the N-terminal kinesin-interacting domain and coiled-coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non-classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re-resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.

Global Epidemiology of Pediatric Traumatic Spine Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: Traumatic spine injury (TSI) leads to significant morbidity and mortality in children. However, the global epidemiology of pediatric TSI is currently unknown. We conducted a systematic review and meta-analysis to estimate the global incidence of pediatric TSI and the burden of cases. METHODS: PubMed, Embase, and Scopus were searched for reports in June 2021 and updated in March 2023 with no restrictions on language or year of publication. A meta-analysis was conducted to estimate the global incidence of pediatric TSI and, subsequently, the number of cases of pediatric TSI worldwide and the proportion requiring spine surgery. RESULTS: Of 6557 studies, 25 met the inclusion criteria. Road traffic accidents (64%) were responsible for most cases reported in the literature, followed by falls (18%). The global incidence of TSI in children aged ≤20 years was estimated to be 14.24 of 100,000 children, or 375,734 children, with an estimated 114,975 requiring spine surgery. Across the World Bank income classification groups, lower middle-income countries had the highest pediatric TSI case burden (186,886 cases, with 57,187 requiring spine surgery). Across the World Health Organization regions, countries in the Southeast Asia region had the largest number of projected cases at 88,566, with 27,101 requiring surgical management, followed closely by the African region, with 87,235 projected cases and 26,694 requiring surgical management. CONCLUSIONS: Pediatric TSI represents a large healthcare burden globally. Interventions targeting both injury prevention and strengthening of neurosurgical capacity, especially in low resource settings, are needed to address this global health challenge.

Resection of a ventral intramedullary spinal cord ependymoma through an anterior cervical approach: illustrative case.

BACKGROUND: Although posterior myelotomy leaves patients with dorsal column deficits, few reports have explored the anterior cervical approach for cervical intramedullary tumors. The authors describe the resection of a cervical intramedullary ependymoma through an anterior approach with a two-level corpectomy and fusion. OBSERVATIONS: A 49-year-old male presented with a C3-5 ventral intramedullary mass with polar cysts. Because of the ventral location of the tumor and the added benefit of avoiding a posterior myelotomy and dorsal column deficits, an anterior C4-5 corpectomy offered a direct route and excellent visualization of the ventrally located tumor. After a C4-5 corpectomy, microsurgical resection, and C3-6 anterior fusion with a fibular allograft filled with autograft, the patient remained neurologically intact. Magnetic resonance imaging (MRI) on postoperative day (POD) 1 confirmed gross-total resection. The patient was extubated on POD 2 and was discharged home on POD 4 with a stable examination. At 9 months, the patient developed mechanical neck pain refractory to conservative treatment and underwent a posterior fusion to address pseudarthrosis. MRI at 15 months showed no evidence of tumor recurrence with the resolution of neck pain. LESSONS: An anterior cervical corpectomy provides a safe corridor to access ventral cervical intramedullary tumors and avoids posterior myelotomy. Although the patient required a three-level fusion, we believe the tradeoff of decreased motion compared to dorsal column deficits is preferred.

The current state of global contribution to open access publishing in neurosurgery: A bibliometric analysis.

•The top three countries made up 56.7% of the total open-access (OA) contributions.•Low and lower-middle-income countries are less than 8% of the total OA publications.•There is a disparity in academic voice in the neurosurgical literature.•Disparities potentially affect neurosurgery practice and knowledge dissemination.

A Comparison of Surgery Wait Times and Postoperative Length of Hospital Stay Among Patients with Brain Tumors by Country-Level Income and Healthcare System: A Systematic Review and Meta-analysis.

OBJECTIVE: The current study highlights the differences in surgery wait times and postoperative length of hospital stay (LOS) for brain tumor patients between high income countries (HICs) and low- and middle-income countries (LMICs), and across countries with different payer health systems. METHODS: A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcomes of interest were surgery wait time and postoperative LOS. RESULTS: Fifty-three articles were included totaling 456,432 patients. Five studies discussed surgery wait times and 27 discussed LOS. Three HIC studies reported mean surgery wait time of 4 days (SD not reported), 33 ± 13 days, and 34 ± 39 days, and 2 LMIC studies reported median surgery wait time of 4.6 (1-15) and 50 (13-703) days. Mean LOS was 5.1 days (95% CI: 4.2-6.1 days) from 24 HIC studies and 10.0 days (95% CI: 4.6-15.6 days) from 8 LMIC studies respectively. Mean LOS was 5.0 days (95% CI: 3.9-6.0 days) from countries with mixed payer system, and 7.7 days (95% CI: 4.8-10.5 days) from countries with single payer systems. CONCLUSIONS: There are limited data on surgery wait-times yet slightly more data on postoperative LOS. Despite a wide range of wait times, mean LOS in brain tumor patients tended to be longer in LMICs than HICs and longer for countries with single payer health systems than mixed payer health systems. Further studies are needed to evaluate surgery wait times and LOS for brain tumor patients more accurately.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.