A 25-year-old female presented at 24 weeks and 2 days of gestation with suspected myeloschisis on fetal anatomical survey. Imaging demonstrated an L4-S4 defect, ventriculomegaly, and Chiari type II malformation. Closure remains one of the least standardized components of fetoscopic repair, although small studies have suggested that three-layer repair may reduce CSF leakage, shorten maternal hospitalization, decrease revision rates, and improve Chiari malformation outcomes. The patient underwent a three-port fetoscopic repair with three-layer closure. The authors showcase their approach and advocate for closure technique standardization and its correlation with long-term neurological outcomes in the post-Management of Myelomeningocele Study (MOMS) trial era. The video can be found here: https://stream.cadmore.media/r10.3171/2026.1.FOCVID25217.

BACKGROUND AND OBJECTIVES:Pediatric intracranial aneurysms are rare and often exhibit complex morphologies not amenable to conventional microsurgical reconstruction or endovascular embolization. The Pipeline Embolization Device (PED) is an alternative endovascular treatment of these lesions; however, this device is not approved by the US Food and Drug Administration for use in children due to limited data. Here, we investigated the safety and efficacy of the PED in the pediatric population and compared these outcomes with those in adult populations to expand the current literature in using this device in children. METHODS:A systematic literature review of the PubMed database was performed to identify studies describing the PED in children (18 years or younger). The authors' institutional experience with the device in children was included. Basic analyses of the pediatric cohort were performed. Comparative analyses of safety and efficacy outcomes were conducted between the pediatric cohort and previous adult studies. RESULTS:A total of 114 pediatric patients with 120 intracranial aneurysms were included. Six previous adult studies provided 2098 patients with 2393 aneurysms. There were no significant differences in major complications or neurologic mortality between populations. Pediatric patients were more likely to develop asymptomatic in-stent stenosis (4.2% vs 1.1%, P = .005) and asymptomatic in-stent thrombosis (3.4% vs 0.2%, P < .001). Complete aneurysm occlusion was higher in children on follow-up angiography (92.0% vs 76.7%, P < .001). The incidence rates of major complications and neurologic mortality per patient-month at risk were similar between populations. CONCLUSION:In this study, we found that off-label use of the PED for pediatric intracranial aneurysms has an overall similar safety profile, yet improved efficacy outcome compared with on-label use in adults. These data may help lay the foundation for approval of the PED in treating pediatric intracranial aneurysms.

Importance:Traumatic brain injury (TBI) in children and adolescents is associated with mental and physical health sequelae, including elevated risks of anxiety, depression, persistent headaches, and chronic physical pain. However, factors that may be associated with the risk of these adverse outcomes and with improved recovery remain underexplored. Objective:To examine associations between medically diagnosed TBI and mental (anxiety and depression) and physical (frequent headaches and chronic pain) health outcomes among US children and adolescents aged 6 to 17 years and to evaluate whether these associations vary by level of family resilience. Design, Setting, and Participants:This cross-sectional study used data from the 2022 and 2023 National Survey of Children's Health (NSCH), a nationally representative survey conducted by the US Census Bureau and sponsored by the Health Resources and Services Administration Maternal and Child Health Bureau. The NSCH collects caregiver-reported data on child and adolescent health, family context, and social determinants across all 50 US states and the District of Columbia. This study included children and adolescents aged 6 to 17 years whose parents reported medically diagnosed TBI and a comparison group without medically diagnosed TBI. Children and adolescents with comorbidities were excluded. Survey weights accounted for complex sampling to generate nationally representative estimates. Data analysis was done from June 1 to November 13, 2025. Exposures:Medically diagnosed TBI. Main Outcomes and Measures:Current status and severity of medically diagnosed anxiety, depression, frequent or severe headaches (including migraine headaches), and chronic physical pain. Moderators included adverse childhood experiences, child and adolescent flourishing, and family resilience. Results:Among 33 572 participants, 1195 individuals (3.5%; 47.0% [95% CI, 41.2%-52.9%] female; 46.5% [95% CI, 41.0%-52.0%] aged 15-17 years) had a history of medically diagnosed TBI and 32 377 individuals (96.4%; 54.0% [95% CI, 52.9%-55.1%] female; 51.7% [95% CI, 50.6%-52.8%] aged 6-11 years) had no TBI. Children and adolescents with TBI had a significantly higher prevalence of poor health than those without TBI (eg, current anxiety: 12.9% [95% CI, 9.3%-16.5%] vs 4.7% [95% CI, 4.3%-5.0%]; adjusted prevalence ratio, 1.83 [95% CI, 1.38-2.43]). They had increased odds of current anxiety (adjusted odds ratio [aOR], 1.87 [95% CI, 1.31-2.67]), depression (aOR, 1.98 [95% CI, 1.13-3.47]), frequent headaches (aOR, 7.76 [95% CI, 2.71-22.20]), and chronic pain (aOR, 3.99 [95% CI, 1.81-8.77]). Interaction analyses showed evidence of effect modification on the multiplicative (OR) scale for depression, with higher odds observed at moderate (aOR, 5.64 [95% CI, 1.13-28.20]; P = .04) and low (aOR, 6.41 [95% CI, 1.24-33.20]; P = .03) resilience levels compared with the reference group (no TBI × high resilience). Conclusions and Relevance:In this study, family resilience was associated with variation in the association between TBI and depression. These findings support further investigation of family-focused rehabilitation approaches in prospective studies.

BACKGROUND:Trauma is a leading cause of pediatric morbidity and mortality. Children with traumatic brain injury (TBI), especially with extracranial injuries, can develop immune suppression and subsequent infection. Immune checkpoint pathways, for example, programmed death-ligand 1 (PD-L1), may contribute. We hypothesized that an anti-PD-L1 antibody would safely prevent immune suppression in a juvenile rat model of polytraumatic TBI. METHODS:Juvenile rats underwent TBI plus systemic hemorrhage (TBI/H) or sham injury. Rats received daily injections of saline or anti-PD-L1 (10 μg or 100 μg) for 7 days. Systemic immune function was assessed by measuring TNFα production in whole blood and splenocytes after ex vivo stimulation with lipopolysaccharide. Cytokines were measured by ELISA or proteome array. Immunofluorescence was used to quantify microglia, astrocytes, and neurons in postinjury day (PID) 7 brain tissue. Cognitive function was assessed by behavioral testing on PID 1. RESULTS:TBI/H resulted in lower TNFα response in whole blood and spleen ( p =0.02) versus sham-injured rats. TBI/H rats treated with 100 μg anti-PD-L1 had higher TNFα response in whole blood ( p =0.04) and spleen ( p =0.02) versus TBI/H rats treated with saline. Lower dose anti-PD-L1 had no effect on immune function. Unstimulated plasma was examined using a proteome array, and higher levels of inflammatory mediators were noted on PID 7 in injured animals treated with 100 µg anti-PD-L1 versus saline. The 100 μg anti-PD-L1 group had higher perilesional microglia ( p =0.004) and astrocyte ( p =0.03) counts, as compared with TBI/H+saline. Barnes maze results were not different between injured rats treated with 10 μg anti-PD-L1 versus sham injury, but the 100 μg dose resulted in worse performance ( p =0.007). CONCLUSIONS:Anti-PD-L1 treatment prevented posttraumatic immune suppression but only at a dose that resulted in higher numbers of perilesional microglia and no improvement in spatial memory. As such, PD-L1 blockade may not be a good candidate for safely reversing immune suppression after pediatric TBI. ( J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 The Author(s). Published byWolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.). LEVEL OF EVIDENCE:Not applicable (basic science/animal research).

This brief review focuses on the imaging of the craniocervical junction with particular attention to linear and angular craniometry. It attempts to answer the question of why there are so many measurements and how they are clinically useful. Congenital anomalies of the craniocervical junction will be discussed with an overview of craniocervical junction embryology and development. Entities affecting the craniocervical junction which will be discussed include platybasia, basilar invagination, atlanto-occipital assimilation, and assorted congenital anomalies.

BACKGROUND Intracranial pseudoaneurysms are a rare yet treacherous subtype of cerebral aneurysms associated with a high risk of rupture. Left untreated, these lesions exhibit high rates of morbidity and mortality.The advent of flow diversion has shifted the treatment paradigm of these lesions from vessel sacrifice to vessel reconstruction. However, experience with flow diversion of distal intracranial pseudoaneurysms remains limited. OBSERVATIONS A 14-year-old female was found to have a distal M3 segment middle cerebral artery pseudoaneurysm on routine noninvasive follow-up imaging following resection of a pleomorphic xanthoastrocytoma. Diagnostic cerebral angiography confirmed the presence of an 8-mm pseudoaneurysm in the distal left M3 middle cerebral artery. Flow diversion of the parent vessel was performed with a Pipeline Vantage embolization device. Completion angiography demonstrated early contrast stasis within the pseudoaneurysm with excellent wall apposition of the flow diverter. The patient tolerated the procedure well and was discharged on aspirin and ticagrelor for 6 months. LESSONS Intracranial lesions suspicious for pseudoaneurysms on noninvasive imaging should be evaluated with diagnostic cerebral angiography. Intradural pseudoaneurysms are challenging lesions to treat with open cerebrovascular and endovascular approaches. Flow diversion of distal M3 middle cerebral artery pseudoaneurysms is a safe, feasible, and efficacious treatment option for these rare lesions. https://thejns.org/doi/10.3171/CASE25989

Background Older persons comprise most traumatic brain injury (TBI)-related hospitalizations and deaths and are particularly susceptible to fall-induced TBIs. The combination of increased frailty and susceptibility to clinical decline creates a significant ongoing challenge in the management of geriatric TBI. As the population ages and co-existing medical conditions complexify, so does the need to improve the quality of care for this population. Utilizing early hospital admission variables, this study will create and validate a multinomial decision tree that predicts the discharge disposition of older patients with fall-related TBI.Methods From the National Trauma Data Bank, we retrospectively analyzed 11,977 older patients with a fall-related TBI (2017-2021). Clinical variables included Glasgow Coma Scale (GCS) score, intracranial pressure monitor use, venous thromboembolism (VTE) prophylaxis, and initial vital signs. Outcomes included hospital discharge disposition re-categorized into home, care facility, or deceased. Data were split into two sets, where 80% developed a decision tree, and 20% tested predictive performance. We employed a conditional inference tree algorithm with bootstrap (B = 100) and grid search options to grow the decision tree and measure discrimination ability using the area under the curve (AUC) and calibration plots.Results Our decision tree used seven admission variables to predict the discharge disposition of older TBI patients. Significant non-modifiable variables included total GCS and injury severity scores, while VTE prophylaxis type was the most important interventional variable. Patients who did not receive VTE prophylaxis treatment had a higher probability of death. The predictive performance of the tree in terms of AUC value (95% confidence intervals) in the training cohort for death, care, and home were 0.66 (0.65-0.67), 0.75 (0.73-0.76), and 0.77 (0.76-0.79), respectively. In the test cohort, the values were 0.64 (0.62-0.67), 0.75 (0.72-0.77), and 0.77 (0.73-0.79).Conclusions We have developed and internally validated a multinomial decision tree to predict the discharge destination of older patients with TBI. This tree could serve as a decision support tool for caregivers to manage older patients better and inform decision-making. However, the tree must be externally validated using prospective data to ascertain its predictive and clinical importance.

Immobilization of the cervical spine at the scene of injury represents standard of care in prehospital management of pediatric trauma patients. Exclusion of injury after formal trauma evaluation and the decision to discontinue immobilization can be straightforward in awake and asymptomatic patients but challenging in preverbal or very young children, patients with severe traumatic brain injury (TBI), intoxicated patients, or patients with otherwise impaired consciousness. This chapter discusses the unique aspects of pediatric cervical spine anatomy, injury patterns, and evaluation. It reviews current practice as well as a summary derived from published protocols providing guidance for cervical spine clearance in children. Any persistent pain or neurologic deficit should prompt evaluation for spinal cord injury without radiographic abnormality (SCIWORA). Most protocols recommend MRI of the cervical spine for this purpose rather than flexion-extension films. Cervical spine immobilization should be continued throughout this process until formal clearance of the cervical spine is obtained.

Traumatic brain injury (TBI) in children is associated with high rates of morbidity and mortality. Nosocomial respiratory infections are common following severe TBI, especially with polytraumatic TBI. Although post-injury immunosuppression has been identified as a potential contributor to nosocomial infection, the underlying mechanism and optimal therapy are poorly understood. In this study, we used a combined model of TBI plus extra-cranial hemorrhage followed by intranasal inoculation with Streptococcus pneumoniae to model the clinical scenario of polytrauma TBI and post-injury infection. Briefly, 28-day (prepubescent) rats received either sham injury or prefrontal controlled cortical impact injury plus removal of 25% of blood volume through femoral cannulation. Saline or 50µg/kg granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered intraperitoneally daily for 2 days. Post-injury immune response was assessed in the blood, spleen, and brain using different immunologic techniques, while bacterial clearance was examined by plating lung tissue. Our results show that GM-CSF enhanced innate immune function by increasing the percentage of blood monocytes expressing elevated levels of MHC II molecules. GM-CSF also significantly increased splenic CD3 + T-cells, compared to the saline-treated injury group. Moreover, increased lung bacterial load (colony-forming units) was significantly reduced with GM-CSF treatment. Treatment with GM-CSF was not associated with an increase in brain glial activation, neuronal loss, or memory dysfunction. This study highlights the potential role of GM-CSF as a therapy to address the increased risk of nosocomial infections following polytraumatic TBI.

Background: Coagulation disturbances and hemorrhage are common in critically ill pediatric patients especially those with intracranial pathology or traumatic brain injury (TBI). Even with therapy directed by laboratory parameters, blood products may fail to effectively correct the underlying coagulation defect. To mitigate these challenges, various adjunctive agents including prothrombin complex concentrates (PCCs) have been used in patients who have coagulation disturbances refractory to standard therapy. However, data regarding the use of PCCs in pediatric-aged patients are limited. Methods and Results: We retrospectively identified 47 critically ill pediatric patients, ranging in age from 1 day to 18 years, with intracranial pathology including TBI who received PCC. The primary clinical indications for four-factor PCC (4F-PCC) were surgical procedures, hemorrhage control, or intracranial pressure monitor placement. A total of 71 doses of 4F-PCC were administered to the 47 patients in the study cohort. The PCC dose ranged from 11 to 75 units/kg (median dose 26 units/kg). The majority of patients (n = 35, 75%) received one dose of 4F-PCC while 12 patients received more than one dose. Following the administration of PCC, there was a correction in laboratory assessment of coagulation function (international normalized ratio and prothrombin time) with a limited effect on partial thromboplastin time. Because of the severity of illness and limitations of controlling confounding variables in a retrospective study, additional information on the direct effects of 4F-PCC on patient outcome including blood product utilization was limited. Conclusions: Given the increasing use of PCC in pediatric-aged patients and its potential utility in life-threatening scenarios, additional clinical trials are needed to define clinical indications, dosing regimens, and optimal monitoring techniques. Int J Clin Pediatr. 2024;13(1):8-13 doi: https://doi.org/10.14740/ijcp527

Early post-traumatic seizures (PTS) are associated with worse outcomes in children with traumatic brain injury (TBI). Our aim was to identify the association between continuous electroencephalogram (cEEG) characteristics and early PTS risk following pediatric severe TBI. We also evaluated the relationship between cEEG background features and outcomes. A single-center retrospective cohort study was performed on children between 0 and 18 years of age admitted to the pediatric intensive care unit from 2016 to 2019 with severe TBI and cEEG monitoring within 7 days of injury. Raw cEEG tracings were reviewed by an epileptologist in accordance with American Clinical Neurophysiology Society (ACNS) Critical Care EEG terminology. Univariate comparisons were made between children with and without early PTS, as well as between those with and without varying cEEG background features. Eighteen children (31%) of the 59 included had early PTS. Interictal abnormalities, inclusive of sporadic spikes and sharp waves, rhythmic delta activity, or lateralized periodic discharges (LPDs) were more common among children with seizures (100 vs. 22%; p < 0.01). LPDs were also more common in the seizure group (44 vs. 2%; p < 0.01). Background discontinuity was associated with worse Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) scores at discharge and 3-, 6-, and 12-month post-discharge ( p < 0.01). Lack of reactivity was also associated with worse GOS-E Peds scores at 3-, 6-, and 12-month post-discharge ( p < 0.01). Interictal abnormalities and LPDs were each associated with early PTS following pediatric severe TBI. Larger studies should evaluate if high-risk patients would benefit from prolonged cEEG monitoring and/or more aggressive anti-seizure prophylaxis. Discontinuity and lack of variability were associated with worse outcomes. Future studies should attempt to clarify their role as potential early markers of prognosis.

Abstract BACKGROUND VHL is a rare cancer predisposition syndrome which affects many organ systems, leading to renal clear cell carcinoma (RCC), pheochromocytoma, retinal angiomas and CNS hemangioblastomas. Surgical resection has traditionally been the mainstay of treatment of VHL-associated tumors. In 2021, belzutifan, a Hypoxia Inducible Factor 2-alpha inhibitor was approved by the Food and Drug Administration for the treatment of VHL-associated RCC based on efficacy in adults. There is a paucity of data in pediatric VHL patients with hemangioblastoma treated with this novel agent. Herein we present such a case. CASE A 15-year-old male, diagnosed with VHL caused by a de novo germline mutation at the age of 12, was found to have a left craniocervical junction lesion consistent with a hemangioblastoma on surveillance MRI. The lesion demonstrated growth upon serial imaging but remained asymptomatic. Due to location, the patient was started on medical treatment using once daily oral belzutifan (120mg) continuously, sperm banking was performed prior to initiation of therapy. Hematologic and metabolic laboratory values were monitored, in addition to regular physical examinations including blood oxygen saturation recordings. The first MRI on therapy (3 months after treatment started) demonstrated a major radiologic response using RANO criteria. Treatment has been overall very well tolerated with few treatment-related toxicities limited to CTCAE v5 grade 1 fatigue and grade 2 anemia. No dose reductions or interruptions were required. The patient remains on therapy and has completed 11 months of treatment with further reduction in the size of this target lesion. CONCLUSION Hemangioblastomas are preponderantly characterized by their highly vascular nature making surgical resection in some cases arduous depending on location. This unique pediatric case adds to the growing evidence that therapy with belzutifan may be a safe and efficacious option for VHL-associated CNS Hemangioblastomas. Prospective studies in children are needed.

Background Predictive scales have been used to prognosticate long-term outcomes of traumatic brain injury (TBI), but gaps remain in predicting mortality using initial trauma resuscitation data. We sought to evaluate the association of clinical variables collected during the initial resuscitation of intubated pediatric severe patients with TBI with in-hospital mortality.Methods Intubated pediatric trauma patients <18 years with severe TBI (Glasgow coma scale (GCS) score ≤8) from January 2011 to December 2020 were included. Associations between initial trauma resuscitation variables (temperature, pulse, mean arterial blood pressure, GCS score, hemoglobin, international normalized ratio (INR), platelet count, oxygen saturation, end tidal carbon dioxide, blood glucose and pupillary response) and mortality were evaluated with multivariable logistic regression.Results Among 314 patients, median age was 5.5 years (interquartile range (IQR): 2.2–12.8), GCS score was 3 (IQR: 3–6), Head Abbreviated Injury Score (hAIS) was 4 (IQR: 3-5), and most had a severe (25-49) Injury Severity Score (ISS) (48.7%, 153/314). Overall mortality was 26.8%. GCS score, hAIS, ISS, INR, platelet count, and blood glucose were associated with in-hospital mortality (all p<0.05). As age and GCS score increased, the odds of mortality decreased. Each 1-point increase in GCS score was associated with a 35% decrease in odds of mortality. As hAIS, INR, and blood glucose increased, the odds of mortality increased. With each 1.0 unit increase in INR, the odds of mortality increased by 1427%.Conclusions Pediatric patients with severe TBI are at substantial risk for in-hospital mortality. Studies are needed to examine whether earlier interventions targeting specific parameters of INR and blood glucose impact mortality.

This is a protocol to describe the materials and methods utilized to perform preclinical traumatic brain injury (TBI) with polytrauma for the express purpose of inducing post-injury immune suppression. This protocol, as presented, has been validated in juvenile (post-natal day 28) rats of the Sprague Dawley breed. Our results have shown that this model leads to early immune suppression as noted in innate1 and adaptive2 immune function. The posting of this protocol is part of the mission of the PREClinical Interagency reSearch resourcE-TBI (PRECISE-TBI, precise-tbi.org) to improve clinical translation of therapeutics by providing an online catalog and standardized protocols to reduce the variability of model usage between laboratories.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

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Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world-wide survey to ISEV members to assess methods considered 'best practices' for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.