The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus.

The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highly similar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSF production from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinase SPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.

Regional variations in morbidity and mortality among neonates with intraventricular hemorrhage: a national database analysis.

BACKGROUND: Intraventricular hemorrhage (IVH) often affects newborns of low gestational age and low birth weight, requires critical care for neonates, and is linked to long-term neurodevelopmental outcomes. Assessing regional differences in the U.S. in care for neonatal IVH and subsequent outcomes can shed light on ways to mitigate socioeconomic disparities. METHODS: Using the 2016-2019 National Inpatient Sample (NIS), patients with a primary diagnosis of IVH were identified using ICD-10-CM codes. A retrospective cohort study was conducted with patients stratified by hospital region. Demographics, comorbidities, presentation, intraoperative variables, and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as > 75th percentile of LOS), exorbitant cost (defined as > 75th percentile of cost), and mortality. RESULTS: Included in this study were 1630 newborns with IVH. A larger portion of patients in the South and Midwest were Black, compared to the Northeast and West (Northeast: 12.2% vs Midwest: 30.2% vs South: 22.8% vs West: 5.8%, p < 0.001), while a greater percentage of patients in the West and South were Hispanic (Northeast: 7.3% vs Midwest: 9.5% vs South: 22.8% vs West: 36.2%, p < 0.001). LOS was similar among all regions. Factors associated with prolonged LOS included hydrocephalus and CSF diversions. Median total cost of admission was highest in the West, while the South was associated with decreased odds of exorbitant cost. LOS was associated with exorbitant cost, and large bed-volume hospital, VLBW, and permanent CSF shunt were associated with mortality. CONCLUSIONS: Demographic variables, but not presenting or intraoperative variables, differed among regions, pointing to possible geographic health disparities. The West had the highest total cost of admission, while the South was associated with reduced odds of exorbitant admission costs.

Reduced racial disparities among newborns with intraventricular hemorrhage.

INTRODUCTION: Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. METHODS: Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. RESULTS: Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. CONCLUSIONS: Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Sociodemographic Disparities and Postoperative Outcomes Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database.

OBJECTIVE: The objective of this study was to assess whether race and ethnicity are independent predictors of inferior postoperative clinical outcomes, including increased complication rates, extended length of stay (LOS), and unplanned 30-day readmission following cranial vault repair for craniosynostosis. METHODS: A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients under 2 years of age undergoing cranial vault repair for craniosynostosis between 2012 and 2021 were identified using the International Classification of Diseases-9/10 and Current Procedural Terminology codes. Patients were dichotomized into 4 cohorts: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and other. Only patients with available race and ethnicity data were included in this study. Patient demographics, comorbidities, surgical variables, postoperative adverse events, and hospital resource utilization were assessed. Multivariate logistic regression analysis was used to assess the impact of race on complications, extended LOS, and unplanned readmissions. RESULTS: In our cohort of 7764 patients, 72.80% were NHW, 8.44% were NHB, 15.10% were Hispanic, and 3.67% were categorized as "other." Age was significantly different between the 4 cohorts ( P <0.001); NHB patients were the oldest, with an average age of 327.69±174.57 days old. Non-Hispanic White experienced the least adverse events while NHB experienced the most ( P =0.01). Total operative time and hospital LOS were shorter for NHW patients ( P <0.001 and P <0.001, respectively). Rates of unplanned 30-day readmission, unplanned reoperation, and 30-day mortality did not differ significantly between the 4 cohorts. On multivariate analysis, race was found to be an independent predictor of extended LOS [NHB: adjusted odds ratio: 1.30 (1.04-1.62), P=0.021; other: 2.28 (1.69-3.04), P =0.005], but not of complications or readmission. CONCLUSIONS: Our study demonstrates that racial and ethnic disparities exist among patients undergoing cranial vault reconstruction for craniosynostosis. These disparities, in part, may be due to delayed age of presentation among non-Hispanic, non-White patients. Further investigations to elucidate the underlying causes of these disparities are necessary to address gaps in access to care and provide equitable health care to at-risk populations.

Associated Risk Factors for Extended Operative Time Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The aim of this study was to identify the factors associated with extended operative time (EOT) for pediatric patients with craniosynostosis undergoing cranial vault remodeling (CVR). METHODS: A retrospective cohort study was performed using the 2012 to 2021 American College of Surgeons National Surgical Quality Improvement Program Pediatric--Pediatric database. Pediatric patients below 2 years old with craniosynostosis who underwent CVR were identified using Current Procedural Terminology and International Classification of Diseases-9/10 codes. Patients were dichotomized according to whether they encountered an EOT, which was defined as operative time greater than the 75th percentile for the entire cohort (246 min). Patient demographics, comorbidities, intraoperative variables, postoperative adverse events, and health care resource utilization were assessed. Multivariate logistic regression analysis was utilized to identify predictors of EOT and length of stay. RESULTS: In the cohort of 9817 patients undergoing CVR, 24.3% experienced EOT. The EOT cohort was significantly older and less likely to be non-Hispanic White. Patient comorbidities and surgical adverse events were more frequent among the EOT cohort, including proportions of postoperative surgical site infections. Independent predictors for EOT included age, racial identity, weight, and a higher American Society of Anesthesiologists classification. EOT was found to be an independent predictor for prolonged hospitalization EOT [adjusted odds ratios: 0.78 (0.44-1.13), P<0.001]. CONCLUSIONS: This study demonstrates that age, race, and comorbidities contribute to EOT after CVR for craniosynostosis. EOT is independently associated with a longer length of stay. Additional investigations to further understand the risk factors and impacts of extended EOT are warranted to improve patient outcomes.

Associated Risk Factors for Extended Length of Stay Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database.

OBJECTIVES: The aim of this study was to identify the factors associated with extended length of stay (LOS) for pediatric patients with craniosynostosis undergoing cranial vault remodeling (CVR). METHODS: A retrospective cohort study was performed using the 2012 to 2021 American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients below 2 years old with craniosynostosis who underwent CVR were identified using Current Procedural Terminology and International Classification of Diseases-9/10 codes. Patients were dichotomized according to whether they encountered an extended postoperative hospital LOS, which was defined as LOS greater than the 75th percentile for the entire cohort (4 days). Patient demographics, comorbidities, intraoperative variables, postoperative adverse events, and health care resource utilization were assessed. Multivariate logistic regression analysis was utilized to identify predictors of prolonged LOS. RESULTS: In our cohort of 9784 patients, 1312 (13.4%) experienced an extended LOS. The extended LOS cohort was significantly older than the normal LOS cohort (normal LOS: 225.1±141.8 d vs. extended LOS: 314.4±151.7 d, P<0.001) and had a smaller proportion of non-Hispanic white patients (normal LOS: 70.0% vs. extended LOS: 61.2%, P<0.001). Overall, comorbidities and adverse events were significantly higher in the extended LOS cohort than the normal LOS cohort. On multivariate logistic regression, independent associations of extended LOS included age, race and ethnicity, weight, American Society of Anesthesiologists classification, impaired cognitive status, structural pulmonary abnormalities, asthma, and neuromuscular disorders. CONCLUSIONS: This study demonstrates that age, race, comorbidities, and perioperative complications contribute to extended LOS after CVR for craniosynostosis. Further investigations to further elucidate the risk factors of extended LOS is warranted to optimize patient outcomes.

Virtual Surgical Planning in Craniosynostosis Reduces Operative Time and Length of Stay for Cranial Vault Remodeling.

Cranial vault remodeling (CVR) with and without frontal orbital advancement remodels the skull in craniosynostosis. Virtual surgical planning (VSP) for preoperative planning has been previously shown to be effective in CVR. In this study, the authors aimed to evaluate the impact of VSP on operative and perioperative efficiency for craniosynostosis surgery. A retrospective chart review was conducted of patients with craniosynostosis who underwent CVR. Patient demographics, perioperative variables, use of VSP, and complications were obtained. Perioperative variables collected include operative time and length of stay. An independent t test was used to compare variables from patients who had surgery with VSP and patients who did not. Records were available for 126 patients with craniosynostosis who underwent CVR of whom 79 (62.7%) utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39). Surgeries planned using VSP demonstrated a decreased operative time of 1.3 hours (3.7±1.1 versus 5.0±1.1 h, P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no differences in complication rates of dehiscence, infection, returns to the operating room, or 30-day readmission. These trends were similar among patients who underwent fronto-orbital advancement in addition to CVR. Virtual surgical planning was associated with decreased operative time and length of stay for patients with craniosynostosis and comparable complication rates. Virtual surgical planning is an effective tool for reducing anesthetic exposure time.

Protein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination.

We report the case of a patient with severe progressive epilepsy and peripheral neuropathy and a novel de novo inactivating variant (p.E79X) in Protein Kinase D1 (PKD1). Using CRISPR/Cas9, we engineered the homologous variant in mice and showed that in the homozygote mouse, it recapitulated the patient peripheral nerve hypermyelination pathology. The lethality of the homozygote mouse prevented us from performing an assessment of locomotor behavior. The mutant heterozygote mouse; however, exhibited a significant increase in kainate-induced seizure activity over wild-type mice, supporting the hypothesis that the PKD1 variant is a candidate for the cause of the patient epilepsy. Because PKD1 was previously identified in a kinomic screen as an interacting partner of the K-Cl cotransporter 3 (KCC3), and since KCC3 is involved in peripheral nerve disease and brain hyperexcitability, one possible mechanism of action of PKD1 in disease is through KCC3. We show that catalytically inactive PKD1 stimulates KCC3 activity, consistent with tonic relief of inhibitory phosphorylation. Our findings implicate a novel role for PKD1 in the human nervous system, and uncover a mechanism that could serve as a potential target to promote nervous system myelination.

Pre-operative headaches and obstructive hydrocephalus predict an extended length of stay following suboccipital decompression for pediatric Chiari I malformation.

PURPOSE: For young children and adolescents with Chiari malformation type I (CM-I), the determinants of extended length of hospital stay (LOS) after neurosurgical suboccipital decompression are obscure. Here, we investigate the impact of patient- and hospital-level risk factors on extended LOS following surgical decompression for CM-I in young children to adolescents. METHODS: The Kids' Inpatient Database year 2012 was queried. Pediatric CM-I patients (6-18 years) undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree patient comorbidities or post-operative complications correlated with extended LOS. RESULTS: A total of 1592 pediatric CM-I patients were identified for which 328 (20.6%) patients had extended LOS (normal LOS, 1264; extended LOS, 328). Age, gender, race, median household income quartile, and healthcare coverage distributions were similar between the two cohorts. Patients with extended LOS had significantly greater admission comorbidities including headache symptoms, nausea and vomiting, obstructive hydrocephalus, lack of coordination, deficiency anemias, and fluid and electrolyte disorders. On multivariate logistic regression, several risk factors were associated with extended LOS, including headache symptoms, obstructive hydrocephalus, and fluid and electrolyte disorders. CONCLUSIONS: Our study using the Kids' Inpatient Database demonstrates that presenting symptoms and signs, including headaches and obstructive hydrocephalus, respectively, are significantly associated with extended LOS following decompression for pediatric CM-I.

Functional Network Development in Sagittal Craniosynostosis Treated With Whole Vault Cranioplasty.

INTRODUCTION: In this study, the authors seek to clarify the neurological changes before and after whole vault cranioplasty (WVC) in patients born with sagittal craniosynostosis. METHODS: A case control study design was performed that included thirty functional MRI scans, from 25 individual patients. Functional MRI and diffusion tension imaging data were analyzed with BioImageSuite (Yale University, USA). 9 functional brain networks were analyzed, with appropriate correlated functional regions of the brain and utilized for analysis. RESULTS: Comparing functional MRI the infants after WVC versus infants before WVC group, the after WVC group demonstrated an increased connectivity in the left frontoparietal, secondary (V2), and third (V3) visual networks (P < 0.001). The right frontoparietal (RFPN) had decreased connectivity (P < 0.001). There is also a decrease and increase in anisotropy in the cingulum and precuneus despite surgery, respectively (P < 0.05). Adolescents treated with WVC compared to controls, demonstrated an increased connectivity in the salience and decreased connectivity in the RFPN relative to adolescent controls. CONCLUSIONS: Patients born with sagittal craniosynostosis have different connections in infancy in most of the defined cerebral networks compared to controls. After surgery, there are specific connectivity changes that occur in the RFPN, left frontoparietal, V2, and V3 networks, which are areas associated with executive function and emotional control. Changes identified in white matter tract microstructure connections could be influential in changes in functional connectivity. Although, as a child with sagittal craniosynostosis develops, much of the abnormal network connections, seen in infancy preoperatively, corrects to some degree after surgery. However, some aberrancies in the salience and RFPN networks remain potentially affecting executive functioning.

Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib.

Efficacy of BRAF V600E targeted therapies in brain tumors harboring the mutation has been shown in several case reports and is currently being studied in larger clinical trials. Monotherapy with vemurafenib has been associated with significant side effects, including rashes, papillomas, and squamous cell carcinomas. Here we describe an adolescent female with anaplastic ganglioglioma and significant skin reaction to vemurafenib with subsequent tumor response and tolerance to the BRAF/MEK inhibitor combination of dabrafenib and trametinib without recurrence of previous reaction.

Non-syndromic single-suture craniosynostosis in triplets.

INTRODUCTION: Craniosynostosis is the premature fusion of one or more cranial sutures. The cause of non-syndromic craniosynostosis has been attributed to a complex interaction among genetic, epigenetic, and environmental factors. Increased concordance rates in monozygotic twins support a genetic etiology while a concordance rate less than 100% suggests environmental and/or epigenetic influences. Here, we describe the first reported occurrence of all three children in a triplet set with non-syndromic single-suture craniosynostosis. CASE REPORT: The dichorionic triamniotic triplets were the product of a non-consanguineous marriage delivered at 35 weeks' gestation by a 38-year-old mother and consisted of a monochorionic-diamniotic pair (A and B) and a fraternal triplet (C). Three-dimensional computed tomography scans confirmed sagittal synostosis in A and B and metopic synostosis in C. All patients underwent endoscopic strip craniectomy and were discharged on the second postoperative day with helmet orthoses. Comparative genetic hybridization (CGH) and whole-exome sequencing (WES) failed to identify pathogenic copy number variants or gene mutations, respectively. DISCUSSION AND CONCLUSION: The results of the genetic testing suggest the possibility of a rare variant contributing to the risk of midline craniosynostosis shared among the triplets, with potential modifiers at other genetic loci affecting the phenotype. We speculate mutations at loci within non-coding regions not captured by our genetic analysis may have been involved. Moreover, epigenetic factors as well as environmental factors including, but not limited to, in utero head constraint could have contributed to the observed phenotype.

A Review of Cerebral Shunts, Current Technologies, and Future Endeavors.

Objective. The use of cerebrospinal shunts is the standard of care for hydrocephalus. However, shunts are extremely vulnerable to failure and lack noninvasive methods to monitor their viability. We review current shunt technologies and attempts to improve their function. Methods. A PubMed search was performed to find literature on shunts and shunt function. Company brochures and websites were also used. Results. Fixed and variable pressure valves from four major companies are discussed. Also reviewed are siphon resistive devices, intracranial pressure sensors, and recent attempts on the development of cerebrospinal fluid sensors, including a micromechanical flow sensor we have recently developed. Conclusions. While variable pressure valves and siphon resistive devices have both had considerable success in dealing with variable intracranial pressure, a more sophisticated, continuous monitoring system is needed to ensure shunt viability and patient safety. An integrated flow sensor may provide the ability to track fluid flow and determine shunt functionality.

Primary spinal myxopapillary ependymoma in the pediatric population: a study from the Surveillance, Epidemiology, and End Results (SEER) database.

Primary spinal myxopapillary ependymomas (MPE) in children are extremely rare. We examined the patient demographics, treatment modalities, and the associated outcomes of children with MPE using the Surveillance, Epidemiology, and End Results (SEER) national cancer database to gain a better understanding of these tumors. The SEER database (1973-2012) was used to analyze patients 21 years of age and younger with histologically confirmed MPE localized to the spinal cord or cauda equina. We analyzed patient demographics, extent of surgical resection, and radiation treatment. Overall survival was calculated using the Kaplan-Meier method. Statistical significance was defined as p < 0.05, with all data analyzed in IBM SPSS Statistics 21. 122 pediatric patients met inclusion criteria. The median age was 16 years (range 0-21) with 63 % male and 87 % Caucasian. The mean follow-up time was 4.5 years (95 % CI 3.93-5.07). Overall survival at 5 and 10 years was 97 and 95 %, respectively. We found 37 % underwent gross-total resection (GTR), 36 % subtotal resection (STR), and 27 % biopsy only. Patients who received GTR alone (n = 37) had a statistically significant increase in overall survival compared to those who received STR plus adjuvant radiation (n = 20) (Χ2 = 5.9, p < 0.05). To our knowledge, this is the largest survival analysis of pediatric patients with MPE. Overall survival is excellent at the 5 and 10-year time points; however, GTR should be the goal of treatment when possible. For patients with MPE, future studies should focus on longer follow-up, the role of radiation, and the therapeutic approach at tumor recurrence.

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

Influence of affective disorders on outcomes after suboccipital decompression for adult Chiari I malformation.

INTRODUCTION: Affective disorders (AD) have been shown to influence patient outcomes and healthcare resource utilization across several pathologies, though this relationship has not been described in patients with Chiari I malformations (CM-I). The aim of this study was to determine the impact of comorbid AD on postoperative events and healthcare resource utilization in adults following suboccipital decompression for CM-I. METHODS: A retrospective study was performed using the 2016-2019 National Inpatient Sample database. Adults who underwent suboccipital decompression for CM-I were identified using ICD-10-CM codes. Patients were stratified into two cohorts, those with AD and those without (No AD). Patient demographics, comorbidities, operative characteristics, perioperative adverse events (AEs), and healthcare resource utilization were assessed. Multivariate logistic regression analyses were used to identify independent predictors of prolonged length of stay (LOS), exorbitant admission costs, and non-routine discharge (NRD). RESULTS: A total of 3985 patients were identified, of which 2780 (69.8%) were in the No AD cohort and 1205 (30.2%) were in the AD cohort. Patient demographics were similar, except for a greater proportion of Female patients than the No AD cohort (p = 0.004). Prevalence of some comorbidities varied between cohorts, including obesity (p = 0.030), ADHD (p < 0.001), GERD (p < 0.001), smoking (p < 0.001), and chronic pulmonary disease (p < 0.001). The AD cohort had a greater proportion of patients with 1-2 (p < 0.001) or ≥ 3 comorbidities (p < 0.001) compared to the No AD cohort. A greater proportion of patients in the AD cohort presented with headache compared to the No AD cohort (p = 0.003). Incidence of syringomyelia was greater in the No AD cohort (p = 0.002). A greater proportion of patients in the No AD cohort underwent duraplasty only (without cervical laminectomy) compared to the AD cohort (p = 0.021). Healthcare resource utilization was similar between cohorts, with no significant differences in mean LOS (No AD: 3.78 ± 3.51 days vs. 3.68 ± 2.71 days, p = 0.659), NRD (No AD: 3.8% vs. AD: 5.4%, p = 0.260), or mean admission costs (No AD: $20,254 ± 14,023 vs. AD: $29,897 ± 22,586, p = 0.284). On multivariate analysis, AD was not independently associated with extended LOS [OR (95%CI): 1.09 (0.72-1.65), p = 0.669], increased hospital costs [OR (95%CI): 0.98 (0.63-1.52), p = 0.930], or NRD [OR (95%CI): 1.39 (0.65-2.96), p = 0.302]. CONCLUSION: Our study suggests that the presence of an AD may not have as much of an impact on postoperative events and healthcare resource utilization in adult patients undergoing Chiari decompression. Additional studies may be warranted to identify other potential implications that AD may have in other aspects of healthcare in this patient population.

Insurance Disparities in Patient Outcomes and Healthcare Resource Utilization Following Neonatal Intraventricular Hemorrhage.

BACKGROUND: Within the field of pediatric neurosurgery, insurance status has been shown to be associated with surgical delay, longer time to referral, and longer hospitalization in epilepsy treatment, myelomeningocele repair, and spasticity surgery.1,2 The aim of this study was to investigate the association of insurance status with inpatient adverse events (AEs), length of stay (LOS), and costs for newborns diagnosed with intraventricular hemorrhage (IVH). METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Patients with a primary diagnosis of intraventricular hemorrhage were identified using ICD-10-CM diagnostic and procedural codes. Patients were categorized based on insurance status: Medicaid or Private Insurance (PI). Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as >75th percentile of LOS) and exorbitant cost (defined as >75th percentile of cost). RESULTS: Demographics differed significantly between groups, with the majority of newborns in the PI cohort being White (Medicaid: 35.8% vs. PI: 60.3%, P < 0.001) and the majority of Medicaid patients being in the 0-25th quartile of household income (Medicaid: 40.9% vs. PI: 12.9%, P < 0.001). While insurance status was not independently associated with increased odds of extended LOS or exorbitant cost, Medicaid patients had a greater mean LOS and total cost of admission than PI patients. CONCLUSIONS: Demographic characteristics, mean LOS, and mean total cost differed significantly between Medicaid and PI patients, indicating potential disparities based on insurance status. However, insurance status was not independently associated with increased healthcare utilization, necessitating further research in this area of study.

High inpatient-opioid consumption predicts extended length of hospital stay in patients undergoing spinal fusion for adolescent idiopathic scoliosis.

OBJECTIVES: Opioids are common medications used following spine surgery. However, few studies have assessed the impact of increased inpatient-opioid consumption on outcomes following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). The aim of this study was to determine the impact of increased inpatient-opioid consumption on hospital length of stay (LOS) following PSF for AIS. METHODS: A retrospective cohort study was performed using the Premier Healthcare Database (2016-2017). Adolescent patients (11-17 years old) who underwent PSF for AIS, identified using ICD-10-CM coding, were stratified by inpatient MME (morphine milligram equivalent) consumption into Low (< 25th percentile for the cohort), Medium (25-75th percentile), and High (> 75th percentile) cohorts. Demographics, comorbidities, intraoperative procedures, perioperative adverse events (AEs), length of hospital stay (LOS), non-routine discharge rates, cost of admission, and 30-day readmission rates were assessed. A logistic multivariate regression analysis was performed to determine the association between inpatient MME consumption and extended LOS. RESULTS: Of the 1042 study patients, 260 (24.9%) had Low-MME consumption, 523 (50.2%) had Medium-MME consumption, and 259 (24.9%) had High-MME consumption. A greater proportion of patients in the High cohort identified as non-Hispanic white (Low: 46.5% vs Medium: 61.4% vs High: 65.3%, p < 0.001), while the proportion of patients reporting any comorbidity did not vary across the cohorts (p = 0.940). The number of post-operative AEs experienced also did not vary across the cohorts (p = 0.629). A greater proportion of patients in the High cohort had an extended LOS (Low: 6.5% vs Medium: 8.6% vs High: 19.7%, p < 0.001), while a greater proportion of patients in the Low cohort had an increased cost of admission (Low: 33.1% vs Medium: 20.3% vs High: 26.6%, p < 0.001). The High cohort had increased 30-day readmission rates relative to the Low and Medium cohorts (Low: 0.8% vs Medium: 0.2% vs High: 1.5%, p = 0.049). Non-routine discharge rates did not vary among the cohorts (p = 0.441). On multivariate analysis, High-MME consumption was significantly associated with extended LOS, while Medium-MME consumption was not [Medium: aOR: 1.48, CI (0.83, 2.74), p = 0.193; High: aOR: 4.43, CI (2.47, 8.31), p < 0.001]. CONCLUSIONS: Our study showed that high post-operative-MME consumption was significantly associated with extended LOS in patients undergoing PSF for AIS. In light of these findings, changes to existing protocols that decrease the reliance on opioids for post-operative analgesia are merited to improve patient outcomes and reduce health-care expenditures.

Isolated unilateral alar ligamentous injury: illustrative cases.

BACKGROUND: Isolated unilateral alar ligament injury (IUALI) is a rare and likely underreported occurrence after upper cervical trauma, with only 16 cases documented in the literature to date. Patients generally present with neck pain, and definitive diagnosis is typically made by magnetic resonance imaging (MRI). Unfortunately, likely due in part to its rarity, there are no formal guidelines for the treatment of an IUALI. Furthermore, there is a limited understanding of the long-term consequences associated with its inadequate treatment. OBSERVATIONS: Here, the authors report on three pediatric patients, each found to have an IUALI after significant trauma. All patients presented with neck tenderness, and two of the three had associated pain-limited range of neck motion. Imaging revealed either a laterally deviated odontoid process on cervical radiographs and/or MRI evidence of ligamentous strain or discontinuity. Each patient was placed in a hard cervical collar for 1 to 2 months with excellent resolution of symptoms. A comprehensive review of the literature showed that all patients with IUALI who had undergone external immobilization with either rigid cervical collar or halo fixation had favorable outcomes at follow-up. LESSONS: For patients with IUALI, a moderate course of nonsurgical management with rigid external immobilization appears to be an adequate first-line treatment.

Concurrent impact of de novo mutations on cranial and cortical development in nonsyndromic craniosynostosis.

OBJECTIVE: Nonsyndromic craniosynostosis (nsCS), characterized by premature cranial suture fusion, is considered a primary skull disorder in which impact on neurodevelopment, if present, results from the mechanical hindrance of brain growth. Despite surgical repair of the cranial defect, neurocognitive deficits persist in nearly half of affected children. Therefore, the authors performed a functional genomics analysis of nsCS to determine when, where, and in what cell types nsCS-associated genes converge during development. METHODS: The authors integrated whole-exome sequencing data from 291 nsCS proband-parent trios with 29,803 single-cell transcriptomes of the prenatal and postnatal neurocranial complex to inform when, where, and in what cell types nsCS-mutated genes might exert their pathophysiological effects. RESULTS: The authors found that nsCS-mutated genes converged in cranial osteoprogenitors and pial fibroblasts and their transcriptional networks that regulate both skull ossification and cerebral neurogenesis. Nonsyndromic CS-mutated genes also converged in inhibitory neurons and gene coexpression modules that overlapped with autism and other developmental disorders. Ligand-receptor cell-cell communication analysis uncovered crosstalk between suture osteoblasts and neurons via the nsCS-associated BMP, FGF, and noncanonical WNT signaling pathways. CONCLUSIONS: These data implicate a concurrent impact of nsCS-associated de novo mutations on cranial morphogenesis and cortical development via cell- and non-cell-autonomous mechanisms in a developmental nexus of fetal osteoblasts, pial fibroblasts, and neurons. These results suggest that neurodevelopmental outcomes in nsCS patients may be driven more by mutational status than surgical technique.