Predicting the presence of 4th ventricular outlet obstruction in Chiari I Malformation.

INTRODUCTION: A subset of children with Chiari 1 malformation (CM-1) have a 4th ventricle arachnoid veil-a thin membrane covering the outlet of the 4th ventricle. Studies suggest that failure to disrupt this veil during posterior fossa decompression can reduce the likelihood of syringomyelia resolution. However, there is no reliable method for predicting the presence of the veil without direct surgical exploration. This study aims to evaluate the association between pre-operative symptoms, radiographic measurements, and the arachnoid veil. METHODS: A retrospective review of an institutional database of children evaluated for CM-I was conducted. For patients treated with surgery, operative notes were reviewed to determine if an arachnoid veil was present. Logistic regression was used to test for relationship of clinical variables and radiographic measurements with the presence of an arachnoid veil. RESULTS: Out of 997 children with CM-1, 226 surgical patients were included in the analysis after excluding those with inadequate documentation. An arachnoid veil was found in 23 patients (10.2%). Larger syrinx, spinal canal, and thecal sac diameters were significantly associated with the presence of a veil, with odds ratios of 1.23 (95% CI 1.2-1.48; p = 0.03), 1.27 (95% CI 1.02-1.59; p = 0.03), and 1.35 (95% CI 1.03-1.77; p = 0.03), respectively. No significant associations were found with any signs or symptoms. CONCLUSIONS: Arachnoid veil was present in 10% of cases. Radiographic measurements indicating larger syrinx size were the only variables found to be significantly associated with an arachnoid veil. Exploration of the 4th ventricular outlet is recommended for CM-I decompression in the setting of expansile syringomyelia.

Evaluation of multidisciplinary high-risk pregnancy clinic for myelomeningocele.

INTRODUCTION: A cross-sectional study retrospectively evaluating the perceived usefulness of attending a multi-disciplinary, roundtable, educational prenatal clinic for mothers expecting children with myelomeningocele is presented. METHODS: Mothers who currently have children with SB completed a survey which evaluated their overall preparedness, spina bifida education, delivery plans, surgical expectations, and expectations in terms of quality of life and development. Open comments were also collected. Statistical analysis was performed to identify differences between those who attended prenatal counseling and those who did not. RESULTS: Approximately half of these mothers received some form of prenatal SB counseling. Mothers who attended prenatal counseling reported that they felt more informed and prepared throughout their pregnancy, during the delivery of their child and during their initial hospital stay than mothers who did not. They reported that the roundtable discussions were beneficial, and the education they received was useful in helping them form accurate expectations and feel more at ease. CONCLUSION: This suggests that prenatal counseling and the High-Risk Pregnancy Clinic (HRPC) provides perceived utility to families and mothers and that the HRPC is an effective method of providing prenatal counseling to mothers whose unborn children have been diagnosed with myelomeningocele.

Neurosurgical management of Myelomeningocele in premature infants: a case series.

INTRODUCTION: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 h of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. METHODS: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995-2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. RESULTS: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1-80.8). Five patients were taken for surgery within the recommended 48 h of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria). In both cases of sepsis, patients developed signs and symptoms more than 72 h after birth. Notably, both instances of sepsis occurred unrelated to operative intervention as they occurred before permanent MMC closure. Two patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 h of MMC closure. CONCLUSIONS: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term.

Transition mentorship for spina bifida patients with the JUMP program: a pilot study.

OBJECTIVE: The transition from pediatric to adult care is challenging for patients and families with spina bifida (SB). Lifelong care relationships yield to new care environments that are typically larger, less personal, and less engaged with the nuances of SB care. Adolescence and young adulthood are often characterized by personal and psychological stresses due to factors independent of illness or chronic medical complexity. Surveys have demonstrated that transition is associated with uncertainty, anxiety, and elevated risk of adverse events for many SB patients. To help mitigate this, the authors developed a trial mentorship program between teen patients with SB and undergraduate/medical students. This study analyzes and presents the initial outcomes from this program. METHODS: The authors created the Join, Unite, Motivate, and Prepare (JUMP) program to improve readiness for the transition process. The mentee target population was patients aged 13-19 years receiving care at the authors' SB clinic. Mentors were screened/approved undergraduate/medical students who volunteered to participate and successfully completed online training in mentorship. Upon enrollment, each patient set a combination of clinical, self, and parent/guardian goals using the individualized transition plan. These goals were shared with the mentor, mentee, parent/guardian, and physician. To monitor success, the SB program director routinely met with each mentor to discuss progress made and areas of growth. These included continuous quantitative and qualitative goal setting and failures that needed to be addressed for each agenda. RESULTS: Thirteen mentor-mentee matches were created over 9 months. Of the 13 matches, 6 had more than 5 communications after the initial meeting, and 1 mentor-mentee match is still in contact today. Noted success in the program has been through mentees gaining employment, applying for scholarships, starting college, and connecting with others who are going through similar circumstances. Challenges have arisen through failure to follow-up after the initial office visit, risk with using the virtual platform, and wide geographic dispersion of both mentors and mentees across the authors' state. CONCLUSIONS: Transition from pediatric to adult care for adolescents with SB has proven to be a large hurdle. Easing this process through well-thought-out, interactive processes has the potential to improve readiness, increase patient autonomy, and provide exposure to the adult healthcare community. However, the mentorship model, in the SB setting, has not proven to be the remedy.

The role of a dedicated transition process from pediatric to adult interdisciplinary care for persons with spina bifida.

OBJECTIVE: Interdisciplinary care and pediatric to adult transitional programs have consistently shown medical and social value for individuals with complex medical conditions such as spina bifida (SB). Such interdisciplinary clinics are common in pediatrics but are rarely offered for adults. This survey-based study reports information related to transition, daily pain burden, and satisfaction with care delivery in an adult SB clinic. METHODS: A 23-question survey that was based on empirical observations from the adult SB clinic was formulated, IRB approved, and distributed to adult patients. Many respondents had previously received care at the institution's pediatric SB clinic and completed transition to the adult program. Responses were de-identified, categorized, stored in a secure database, and statistically analyzed using SPSS. RESULTS: Of 245 patients approached, 116 (47%) surveys were completed and analyzed. Those who had a direct transition (defined as a less than 24-month gap in care) from the pediatric to the adult clinic comprised 44% (n = 51) of responders. The alternative group of 56% (n = 65) had a longer gap, disorganized or absent transition, or had pediatric care elsewhere. The study population had an average age of 36 years, had mostly received childhood care at the authors' institution, regardless of whether they made a direct transition or had a gap in care (68%), and held the diagnosis of open myelomeningocele (78%). Overall satisfaction with the clinic experience was high (mean score 9.04 on a 10-point subjective scale). Differences regarding independence in activities of daily living based on transition status were not significant, but on multivariate analysis, those who reported independence in activities of daily living had an almost 4-fold higher odds of daily pain (p = 0.024; OR 3.86, 95% CI 1.19-12.5). The most frequently identified areas for improvement included improved access to care and pain control. CONCLUSIONS: Pediatric transitional processes and interdisciplinary clinics may contribute to improved patient-perceived outcomes and satisfaction with their SB care in comprehensive settings. Further elucidation of barriers to pain control is warranted, in addition to ways in which comprehensive and longitudinal care can improve them.

Hyponatremia after craniotomy in children: a single-institution review.

PURPOSE: Hyponatremia after craniotomy can be associated with increased morbidity. However, the incidence of and factors associated with post-craniotomy hyponatremia in children are not known. METHODS: We performed a retrospective cohort study of patients aged 0-21 years who underwent craniotomy in 2017-2019 at a single center to determine the incidence of and to identify risk factors for hyponatremia after craniotomy. Indications for craniotomy included tumors (excluding craniopharyngioma), epilepsy, intracranial infection, trauma, craniofacial, suboccipital decompression for the treatment of Chiari malformation, and cerebrovascular disease. Hyponatremia was defined as a serum sodium level ≤ 135 mEq/L any time during the postoperative hospital stay. Statistical significance was defined a priori at p < 0.05. RESULTS: Postoperative hyponatremia occurred in 61 (25%) of 240 children. On univariate analysis, hyponatremia was associated with younger age (8.5 vs 6.3 years, p = 0.01), use of preoperative anti-epileptic drugs (p = 0.02), need for blood transfusion (p = 0.02), government/private insurance (p = 0.04), and pre-existing hydrocephalus, defined as the requirement for permanent cerebrospinal fluid (CSF) diversion (p = 0.04). On multivariate analysis, only hydrocephalus (OR 2.95, 95% CI 1.03-8.40) remained statistically significant. Hyponatremia most occurred on the first postoperative day, with normonatremia achieved in a median of 14 (IQR 9.8-24.3) h. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3 days, p < 0.01). CONCLUSION: Hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus as an independent risk factor for hyponatremia after craniotomy.

Global strategies for the prevention of neural tube defects through the improvement of folate status in women of reproductive age.

INTRODUCTION: Neural tube defects represent a global public health problem, mainly in countries where effective prevention strategies are not yet in place. The global prevalence of neural tube defects is estimated at 18.6/10,000 (uncertainty interval: 15.3-23.0) live births, where ~ 75% of cases result in under-five mortality. Most of the mortality burden is in low- and middle-income countries. The main risk factor for this condition is insufficient folate levels in women of reproductive age. METHODS: This paper reviews the extent of the problem, including the most recent global information on folate status in women of reproductive age and the most recent estimates of the prevalence of neural tube defects. Additionally, we provide an overview of the available interventions worldwide to reduce the risk of neural tube defects by improving folate status in the population, including dietary diversification, supplementation, education, and fortification. RESULTS: Large-scale food fortification with folic acid is the most successful and effective intervention to reduce the prevalence of neural tube defects and associated infant mortality. This strategy requires the coordination of several sectors, including governments, the food industry, health services providers, the education sector, and entities that monitor the quality of the service processes. It also requires technical knowledge and political will. An international collaboration between governmental and non-governmental organizations is essential to succeed in saving thousands of children from a disabling but preventable condition. DISCUSSION: We propose a logical model for building a national-level strategic plan for mandatory LSFF with folic acid and explain the actions needed for promoting sustainable system-level change.

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.

Neurosurgical Advocacy in the Prevention of Neural Tube Defects: Impacting Global Fortification Policies Through Leadership, Collaboration, and Stakeholder Engagement.

The G4 Alliance and its member organizations formed a delegation that participated in the 76th World Health Assembly (WHA) in 2023, which unanimously adopted the resolution to address micronutrient deficiencies through safe, effective food fortification to prevent congenital disorders such as spina bifida and anencephaly, the first neurosurgery-led resolution since the founding of the World Health Organization. The WHA included other resolutions and side events by the G4 Alliance and other organizations relevant to neurosurgery. An opportunity exists for neurosurgeons to harness the momentum from this resolution to promote initiatives to prevent neurosurgical disease or expand access to neurosurgical care.

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.

Neurosurgical Management of Myelomeningocele in Premature Infants: A Case Series.

Introduction: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 hours of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. Methods: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995-2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. Results: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1 -80.8). Five patients were taken for surgery within the recommended 48 hours of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria), and 2 patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 hours of MMC closure. Conclusions: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term.

Endoluminal Biopsy for Vein of Galen Malformation.

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Development and application of a computable genotype model in the GA4GH Variation Representation Specification.

As the diversity of genomic variation data increases with our growing understanding of the role of variation in health and disease, it is critical to develop standards for precise inter-system exchange of these data for research and clinical applications. The Global Alliance for Genomics and Health (GA4GH) Variation Representation Specification (VRS) meets this need through a technical terminology and information model for disambiguating and concisely representing variation concepts. Here we discuss the recent Genotype model in VRS, which may be used to represent the allelic composition of a genetic locus. We demonstrate the use of the Genotype model and the constituent Haplotype model for the precise and interoperable representation of pharmacogenomic diplotypes, HGVS variants, and VCF records using VRS and discuss how this can be leveraged to enable interoperable exchange and search operations between assayed variation and genomic knowledgebases.

Racial differences in the care of pediatric sagittal craniosynostosis: a single-institution cohort study affecting state Medicaid policy.

OBJECTIVE: Although research has shown the cost-effectiveness of endoscopic versus open repair of sagittal synostosis, few studies have shown how race, insurance status, and area deprivation impact care for these patients. The authors analyzed data from children evaluated for sagittal synostosis at a single institution to assess how socioeconomic factors, race, and insurance status affect the surgical treatment of this population. They hypothesized that race and indicators of disadvantage negatively impact workup and surgical timing for craniosynostosis surgery. METHODS: Medical records of patients treated for sagittal synostosis between 2010 and 2019 were reviewed. Area deprivation index (ADI) and rural-urban commuting area codes, as well as median income by zip code, were used to measure neighborhood disadvantage. Black and White patients were compared as well as patients using Medicaid versus private insurance. RESULTS: Fifty patients were prospectively included in the study. Thirty-one underwent open repair; 19 had endoscopic repair. All 8 (100%) Black patients had open repair, compared to 54.8% of White patients (p = 0.018). Black patients were more likely to use Medicaid compared to White patients (75.0% vs 28.6%, p = 0.019). White patients were younger at surgery (5.5 vs 10.0 months, p = 0.001), and Black patients had longer surgeries (147.5 minutes vs 110.0 minutes, p = 0.021). The median household income by zip code was similar for the two groups. Black patients were generally from areas of greater disadvantage compared to White patients, based on both state and national ADI scores (state: 7.5 vs 4.0, p = 0.013; national: 83.5 vs 60.0, p = 0.013). All (94.7%) but 1 patient undergoing endoscopic repair used private insurance compared to 14 (45.2%) patients in the open repair group (p = 0.001). Patients using Medicaid were from areas of greater disadvantage compared to those using private insurance by both state and national ADI scores (state: 6.0 vs 3.0, p = 0.001; national: 75.0 vs 52.0, p = 0.001). CONCLUSIONS: Because Medicaid in the geographic region of this study did not cover helmeting after endoscopic repair of sagittal synostosis, these patients usually had open repair, resulting in significant racial and socioeconomic disparities in treatment of sagittal synostosis. This research has led to a change in Alabama Medicaid policy to now cover the cost of postoperative helmeting.

Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells.

BACKGROUND: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach. METHODS: To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state. RESULTS: RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm). CONCLUSIONS: MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.

Does subtotal resection ameliorate hypothalamic morbidity in pediatric craniopharyngioma? A 30-year retrospective cohort study.

OBJECTIVE: The optimal extent of resection of craniopharyngiomas to minimize the long-term risks of hypothalamic and endocrine dysfunction (obesity and panhypopituitarism) in children remains uncertain. The purpose of this study was to report long-term outcomes of pediatric patients with craniopharyngioma undergoing surgical treatment and to study rates of endocrinological and hypothalamic dysfunction in association with extent of resection. METHODS: This retrospective study was performed in a cohort of children who underwent resection for craniopharyngioma at Children's of Alabama between 1990 and 2020. The primary outcome was hypothalamic dysfunction defined as a 0.5 increase in body mass index (BMI) Z-score and as a BMI > 2 SDs with or without psychiatric disturbances. Univariable analysis was performed using ANOVA, Wilcoxon rank-sum test, Pearson's chi-square test, and Fisher's exact test as appropriate. Missing data on the primary outcome were handled via multiple imputations. Relative risks were estimated using a multivariable generalized linear model with a priori variables selected using a modified Poisson regression approach with robust error variance to estimate risk ratios. RESULTS: The cohort includes 39 patients (24 girls and 15 boys; age range 1 month-16 years) who underwent resection of craniopharyngioma at the authors' center between 1990 and 2020. The preoperative goal of treatment was cyst decompression (CD) in 5, subtotal resection (STR) in 13, and gross-total resection (GTR) in 21 patients. The median long-term follow-up after surgery was 8.11 years (average 8.21, range 0.4-24.33 years). Univariate analysis demonstrated a statistically significant increase in hypothalamic dysfunction in patients undergoing GTR when compared to those undergoing STR or CD at 1 month postoperatively (p = 0.006) and 6-11 months postoperatively (p = 0.010), but with this difference not persisting beyond 1 year. Multivariable analysis showed patients older than 10 years at time of surgery to be the most affected and at highest risk of developing significant hypothalamic dysfunction. There was no significant difference in pituitary or neurological function between the STR/CD and GTR groups at 12-24 months or at most recent follow-up. There was no significant difference in BMI Z-scores between the STR/CD and GTR groups at 6-12 months or at most recent follow-up. CONCLUSIONS: Both STR and GTR of craniopharyngioma were associated with significant endocrinological sequelae after 1 year. These potential complications should be discussed with patients and their families, and postoperative protocols should include early nutritional and endocrinological interventions with endocrinologist consultation.

Understanding and identifying the needs of parent caregivers of children with hydrocephalus: a qualitative study.

OBJECTIVE: Hydrocephalus is inherently unpredictable. Most parents whose child is diagnosed with hydrocephalus do not anticipate the diagnosis, nor can anyone predict if or when a child's shunt will fail and require emergency surgery. Previous research has shown that children with hydrocephalus and their caregivers experience significant posttraumatic stress symptoms secondary to the diagnosis. This study aims to understand caregiver experiences and needs, identify gaps in resources/support, and determine opportunities to improve care. METHODS: Semistructured interviews were conducted with parent caregivers of children with hydrocephalus to learn about their experiences with the hydrocephalus diagnosis, hospitalizations, surgeries, coping and support, challenges of caring for a child with hydrocephalus, and logistics for a proposed support program. De-identified interviews were audio-recorded, transcribed, and analyzed for themes. RESULTS: Thematic saturation was reached after 17 interviews. Five major themes emerged: 1) coping with the diagnosis, 2) received support, 3) hydrocephalus management, 4) implications for intervention, and 5) psychosocial stressors for caregivers. A top priority was balanced, trustworthy information delivered with compassion and updated throughout the child's life. Caregivers described a variety of coping strategies, but a majority reported a need for support in processing complex emotions and dealing with the uncertainty of their child's hydrocephalus. Most agreed that having a caregiver support network, medical professionals available for referrals and questions, and referrals to support services and therapies would facilitate feeling supported and providing the best care for their children. CONCLUSIONS: Parent caregivers are critical to the health and well-being of children with hydrocephalus, and it is essential to understand their experiences to improve care. Providing well-defined information, psychosocial support, and resources will help to equip parent caregivers to be advocates for their children and to improve both the caregiver and the child's quality of life.

Hemispherectomy Outcome Prediction Scale: a validity study.

OBJECTIVE: Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. METHODS: The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. RESULTS: The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. CONCLUSIONS: While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Global Neurosurgery: Progress and Resolutions at the 75th World Health Assembly.

Neurosurgical advocates for global surgery/neurosurgery at the 75th World Health Assembly gathered in person for the first time after the COVID-19 pandemic in Geneva, Switzerland, in May 2022. This article reviews the significant progress in the global health landscape targeting neglected neurosurgical patients, emphasizing high-level policy advocacy and international efforts to support a new World Health Assembly resolution in mandatory folic acid fortification to prevent neural tube defects. The process of developing global resolutions through the World Health Organization and its member states is summarized. Two new global initiatives focused on the surgical patients among the most vulnerable member states are discussed, the Global Surgery Foundation and the Global Action Plan on Epilepsy and other Neurological Disorders. Progress toward a neurosurgery-inspired resolution on mandatory folic acid fortification to prevent spina bifida-folate is described. In addition, priorities for moving the global health agenda forward for the neurosurgical patient as it relates to the global burden of neurological disease are reviewed after the COVID-19 pandemic.