Characteristics and outcomes of pediatric dural arteriovenous fistulas: a systematic review.

BACKGROUND: Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. METHODS: We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. RESULTS: We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). CONCLUSION: There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.

Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects.

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.

Postoperative seizure freedom after vagus nerve stimulator placement in children 6 years of age and younger.

OBJECTIVE: Food and Drug Administration (FDA) approval for vagus nerve stimulator (VNS) implantation is limited to patients older than 4 years of age with medically refractory partial-onset seizures. In younger children with severe generalized epilepsy, however, VNS implantation remains off-label. In this study, the authors followed up on their previously reported cohort to review the longer-term safety and efficacy of VNS placement in children younger than 6 years with generalized medically refractory epilepsy (MRE), providing the largest cohort with > 2 years of follow-up to date in this age group. METHODS: This was a retrospective observational cohort study of patients younger than 6 years of age with generalized MRE who underwent VNS implantation at a single institution between 2010 and 2020. Inclusion criteria encompassed failure of more than two antiepileptic drugs alone or in combination, neurologist referral for vagus nerve stimulation, informed consent with knowledge of the off-label status in young children, and > 1 year of follow-up. Outcome measures included seizure reduction rate ≥ 50% and postoperative morbidity defined nominally. Statistical analysis was conducted with Stata/SE. RESULTS: Forty-five patients were included: 11 patients younger than 4 years of age and 34 between 4 and 6 years of age. There were no intraoperative complications. Perioperative complications within 1 year occurred in 11% (n = 5) of the patients and included two wound infections, a mild cough, hyperactivity, hoarseness, and 1 patient with persistent surgical site pain. A seizure reduction ≥ 50% was observed in 36.4% (n = 4) of the patients younger than 4 years of age at the 6-month and 1-, 2-, and 5-year follow-ups. In the 4- to 6-year-old cohort, this was observed in 32.4% (n = 11) of the patients at 6 months, 41.2% (n = 14) at 1 year, 38.2% (n = 13) at 2 years, and 41.2% (n = 14) at 5 years. CONCLUSIONS: VNS implantation for patients younger than 4 years of age with generalized onset MRE has not been approved by the FDA. This retrospective study establishes feasibility, illustrates an acceptable safety profile in children younger than 6 years, and demonstrates efficacy comparable to that reported in older patients.

Immunotherapy for Pediatric Brain and Spine Tumors: Current State and Future Directions.

BACKGROUND: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae. SUMMARY: There is a substantial need for the development of new therapeutic approaches, and since the introduction of immunotherapy by immune checkpoint inhibitors, there has been an exponential increase in clinical trials to adopt these and other immunotherapy approaches in children with brain tumors. In this review, we summarize the current immunotherapy landscape for various pediatric brain tumor types including choroid plexus tumors, embryonal tumors (medulloblastoma, AT/RT, PNETs), ependymoma, germ cell tumors, gliomas, glioneuronal and neuronal tumors, and mesenchymal tumors. We discuss the latest clinical trials and noteworthy preclinical studies to treat these pediatric brain tumors using checkpoint inhibitors, cellular therapies (CAR-T, NK, T cell), oncolytic virotherapy, radioimmunotherapy, tumor vaccines, immunomodulators, and other targeted therapies. KEY MESSAGES: The current landscape for immunotherapy in pediatric brain tumors is still emerging, but results in certain tumors have been promising. In the age of targeted therapy, genetic tumor profiling, and many ongoing clinical trials, immunotherapy will likely become an increasingly effective tool in the neuro-oncologist armamentarium.

Predictors and Outcomes of Subdural Hematomas Managed via Subdural Evacuation Port System.

Background: Subacute subdural hematoma (SDH) is a common pathology most frequently affecting older patients and may be treated operatively through burr holes versus craniotomy or minimally invasively with bedside twist drill craniostomy. Less invasive intervention is favored when possible given a frequently comorbid population. The subdural evacuation port system (SEPS) is a popular treatment option that warrants investigation and reporting of its use and outcomes. Methods: A retrospective review of consecutive patients undergoing SEPS drain placement for chronic or mixed density SDH between 2010 and 2021 was conducted. Outcomes of SDH recurrence, need for operating room procedure after SEPS placement, discharge disposition other than home, and modified Rankin Scale score <3 at discharge were modeled with logistic regression using multiple demographic, clinical, and radiographic features. Results: Ultimately, 86 patients (mean age 68) were included in the analysis with 66 (78%) presenting with mixed-density SDHs. Radiographic factors such as hematoma thickness and midline shift were not associated with the need for an operating room procedure after SEPS placement or discharge disposition. However, the presence of septations and mixed-density SDH versus chronic SDH was significantly associated with increased odds of requiring an operative intervention after SEPS placement. Conclusions: Subacute SDHs are a frequent neurosurgical issue in patient populations where less invasive measures are favored. SEPS drainage continues to be an effective treatment option. However, the presence of septations and mixed-density SDHs has a significantly increased odds of requiring surgical intervention that must be considered in the decision to pursue SEPS drainage.

Telemedicine and Spina Bifida Transition: A Pilot Randomized Trial.

OBJECTIVES: Transition of care is the planned movement of adolescents and young adults from pediatric to adult health care. Many studies have demonstrated the importance of an organized transition process. The purpose of this study is to determine the efficacy of a telemedicine intervention for improving transition readiness among adolescents with spina bifida. METHODS: The present study is a randomized, controlled trial, including children 14 years of age and older with myelomeningocele from a multidisciplinary spina bifida clinic. Subjects were randomized to standard care or to an intervention, consisting of video telemedicine contacts at 3, 6, and 9 months from the clinic visit. The primary outcome measure was a change in the Transition Readiness Assessment Questionnaire score from baseline to 1-year follow-up. RESULTS: Twenty-four patients were enrolled in the study and underwent randomization. The mean age at enrollment was 15.8 years. Ten patients (40%) were female, and the majority were White, non-Hispanic (67%). Despite enrolling 24 patients, only 1 patient in the telemedicine group completed any of the planned telemedicine sessions. No other participant completed any telemedicine counseling sessions. The study was stopped early for lack of participation in the intervention. In a single-group, as-treated analysis, there was no significant change in the Transition Readiness Assessment Questionnaire score between enrollment and 1-year follow-up (Δ = 0.36, P = 0.46). However, there were significant improvements in subscores for Managing Medications, Appointment Keeping, and Managing Daily Activities. CONCLUSIONS: The primary finding from this study was very low participation in a telemedicine video follow-up intervention among adolescents with myelomeningocele. Based on these results, this strategy alone is unlikely to significantly improve readiness for transition to adult care.

Stereotactic radiosurgery for ruptured versus unruptured intracranial arteriovenous malformations.

Background: There are a limited data examining the effects of prior hemorrhage on outcomes after stereotactic radiosurgery (SRS). The goal of this study was to identify risk factors for arteriovenous malformation (AVM) rupture and compare outcomes, including post-SRS hemorrhage, between patients presenting with ruptured and unruptured AVMs. Methods: A retrospective review of consecutive patients undergoing SRS for intracranial AVMs between 2009 and 2019 at our institution was conducted. Chi-square and multivariable logistic regression analyses were utilized to identify patient and AVM factors associated with AVM rupture at presentation and outcomes after SRS including the development of recurrent hemorrhage in both ruptured and unruptured groups. Results: Of 210 consecutive patients with intracranial AVMs treated with SRS, 73 patients (34.8%) presented with AVM rupture. Factors associated with AVM rupture included smaller AVM diameter, deep venous drainage, cerebellar location, and the presence of intranidal aneurysms (P < 0.05). In 188 patients with adequate follow-up time (mean 42.7 months), the overall post-SRS hemorrhage rate was 8.5% and was not significantly different between ruptured and unruptured groups (10.3 vs. 7.5%, P = 0.51). There were no significant differences in obliteration rate, time to obliteration, or adverse effects requiring surgery or steroids between unruptured and ruptured groups. Conclusion: Smaller AVM size, deep venous drainage, and associated intranidal aneurysms were associated with rupture at presentation. AVM rupture at presentation was not associated with an increased risk of recurrent hemorrhage or other complication after SRS when compared to unruptured AVM presentation. Obliteration rates were similar between ruptured and unruptured groups.

Prevalence of attention-deficit/hyperactivity disorder and intellectual disability among children with hydrocephalus.

OBJECTIVE: Little is known about the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with hydrocephalus. In this study, the authors assessed the prevalence of ADHD and its association with clinical and demographic factors, including intellectual disability (ID), a potential factor that can confound the diagnosis of ADHD. METHODS: The authors conducted a cross-sectional study of children 6-12 years of age with hydrocephalus using parent telephone surveys. The Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scale were used to screen for ID and ADHD, respectively. Among children without ID, the authors identified those with ADHD and calculated a prevalence estimate and 95% confidence interval (Wald method). Logistic regression analysis was conducted to compare children with ADHD with those without ADHD based on demographics, family income, parental educational, etiology of hydrocephalus, and primary treatment. As a secondary analysis, the authors compared subjects with ID with those without using the same variables. Multivariable analysis was used to identify factors with independent association with ADHD and ID. RESULTS: A total of 147 primary caregivers responded to the telephone questionnaire. Seventy-two children (49%) met the cutoff score for ID (CAIDS-Q). The presence of ID was significantly associated with lower family income (p < 0.001). Hydrocephalus etiology (p = 0.051) and initial treatment (p = 0.06) approached significance. Of children without ID (n = 75), 25 demonstrated a likely diagnosis of ADHD on the NICHQ, yielding a prevalence estimate of 0.33 (95% CI 0.22-0.44). No clinical or demographic variable showed significant association with ADHD. CONCLUSIONS: These data indicate that the prevalence of ADHD among children with hydrocephalus (33%) is higher than among the general population (estimated prevalence in Alabama is 12.5%). ID is also common (49%). Routine screening for ADHD and ID in children with hydrocephalus may help to ensure that adequate resources are provided to optimize functional outcomes across development.

Establishing collaborations in global neurosurgery: The role of InterSurgeon.

The global deficiency in surgical care has been highlighted in the past several years, through the publication of the Lancet Commission on Global Surgery in 2015, the passage of WHA Resolution 68.15, and concerted efforts by advocacy organizations such as the G4 Alliance.Approximately 23,300 additional neurosurgeons are estimated to be needed to address the greater than 5 million essential neurosurgical cases that are not performed annually, most in low- and middle-income countries (LMICs). However, increasing recognition of the ease and feasibility of virtual technology prompted a shift towards virtual modes of communication. InterSurgeon (https://www.intersurgeon.org/), an independent, internet-based social network platform, has allowed for formal connection between global surgery advocates who may have complementary needs and resources.This manuscript aims to: 1) characterize the current progress of InterSurgeon, 2) describe lessons learned from the creation and use of InterSurgeon, and 3) discuss future directions for InterSurgeon. Equitable, well-designed collaborations are central to progress in global neurosurgery. InterSurgeon has catalyzed collaborations within global neurosurgery across world regions and country income status. In addition to its role in facilitating traditional in person collaborations, InterSurgeon will become an increasingly important tool for connecting surgeons worldwide as virtual collaboration and augmented reality training paradigms become important components of global surgery capacity building.

Predictive Factors for Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery: A Single-Center Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is particularly useful for treatment of deep arteriovenous malformations (AVMs) in eloquent territory with a high associated surgical risk. Prior studies have demonstrated high rates of AVM obliteration with SRS (60%-80%) in a latency period of 2-4 years for complete obliteration. Studies have identified several factors associated with successful obliteration of the AVM nidus; however, these present inconsistent and conflicting data. The aim of this single-center study was to examine factors associated with successful obliteration of AVMs treated with SRS. METHODS: A retrospective review was performed of 210 consecutive patients undergoing SRS for brain AVMs between 2010 and 2019. The χ2 test and logistic regression analysis were used to identify patient and AVM factors associated with successful obliteration. RESULTS: Younger age (P = 0.034) and prior embolization (P = 0.012) were associated with complete obliteration. The presence of coronary artery disease was associated with incomplete obliteration (P = 0.04). No AVM characteristics were statistically associated with complete obliteration, although superficial venous drainage (P = 0.08) and frontal location (P = 0.06) trended toward significance. CONCLUSIONS: Successful obliteration of the AVM nidus was significantly associated with younger age and prior embolization. The presence of coronary artery disease negatively affected obliteration rates. These results add to the mixed results seen in the literature and emphasize the need for continued studies to delineate more specific patient and AVM factors that contribute to successful obliteration.

Seizure Rates After Stereotactic Radiosurgery for Cerebral AVMs: A Single Center Study.

OBJECTIVES: Seizure control after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is an area of growing interest, with previous studies reporting up to 70% seizure freedom after treatment. The goals of this study were to identify specific patient and AVM characteristics associated with seizure presentation and seizure outcomes after SRS treatment. METHODS: A retrospective review of consecutive patients undergoing SRS for brain AVMs between 2009 and 2019 at our institution was conducted. Chi-squared and logistic regression analyses were utilized to identify patient and AVM factors associated with preoperative seizure presentation and development of new onset seizures after SRS. RESULTS: Two hundred ten consecutive patients presenting with AVMs treated with SRS were reviewed. Factors associated with seizure presentation included larger AVM size (P = 0.02), superficial venous drainage (P < 0.05), and parietal location (P = 0.04). Of 188 patients with follow-up (90%), 30 patients presented with seizures and 14 (47%) were seizure-free post-SRS. Of 158 patients presenting without seizure, 29 (18%) developed de novo seizures during follow-up. De novo post-SRS seizures were associated with prior craniotomy for resection of AVM (P = 0.04), post-treatment hemorrhage (P = 0.02), parietal location (P = 0.05), adverse effect requiring steroids (P < 0.01), and adverse effect requiring surgery (P < 0.01). CONCLUSIONS: Seizures are a common presentation of brain AVMs and can be treated effectively with SRS. However, seizures can also be a complication of SRS and are associated with post-treatment hemorrhage, edema, and need for future open surgery.

Hydrocephalus in Spina Bifida.

Hydrocephalus is the most important co-morbidity in myelomeningocele from a neurosurgical perspective. Historically, 75-80% of patients with myelomeningocele have required treatment with a shunt but recent advances including intra-uterine myelomeningocele closure and ETV-CPC are reducing this burden. The expression of hydrocephalus differs between patients and across the life span. Hydrocephalus impacts the clinical expression of other important co-morbidities including the Chiari II malformation and tethered spinal cord. Shunt failure is often the key stress to prompt symptomatic worsening of these other conditions. Shunt failure may occur with minimal ventricular change on CT or MRI in Spina Bifida patients. Waiting for radiographic changes in symptomatic SB patients with shunts may result in hydrocephalus related fatalities. It is hypothesized but not proven that shunt failure may contribute to respiratory insufficiency and be a risk factor for sudden death in adult patients with spina bifida. Excellence in hydrocephalus management in MMC is essential for proper care, good outcomes, and quality of life for patients and families.