88 results on '"Strahle JM"'
Search Results
2. Sports after single-suture synostosis surgery: a survey of Synostosis Research Group members.
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Bonfield CM, Alexander AL, Birgfeld CB, Couture DE, David LR, French B, Gociman B, Goldstein JA, Golinko MS, Kestle JRW, Lee A, Magge SN, Pollack IF, Rottgers SA, Runyan CM, Smyth MD, Vyas R, Wilkinson CC, Skolnick GB, Patel KB, and Strahle JM
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- Humans, Surveys and Questionnaires, Male, Female, Plastic Surgery Procedures methods, Infant, Cranial Sutures surgery, Craniosynostoses surgery, Sports, Neurosurgeons
- Abstract
Objective: Patients with a history of surgery for single-suture craniosynostosis (SSC) as an infant often wish to participate in sports later in childhood. However, there are no established guidelines from neurosurgeons and craniofacial surgeons to guide parents in which sports their child should or should not participate. Therefore, this study aimed to evaluate the attitudes and practice patterns of experienced neurosurgeons and craniofacial surgeons regarding the counseling of caregivers of these patients about sports participation., Methods: A survey was administered to neurosurgeons and craniofacial plastic surgeons of the Synostosis Research Group (SynRG), a group of 9 North American institutions, to identify attitudes toward sports participation in patients with past SSC surgery. Survey responses were collected anonymously in REDCap. Questions regarding specific sports participation recommendations for patients who underwent surgery as an infant for SSC with ideal healing and for those who required a delayed cranioplasty were answered. Questions pertained to patients with nonsyndromic SSC without associated Chiari malformation, syrinx, or other intracranial/intraspinal anomalies., Results: Overall, 20 surgeons were invited to participate in the survey, with 18 (90%) (9 neurosurgeons and 9 craniofacial plastic surgeons) fully completing it. Only 1 (5.6%) surgeon counseled against any sports participation for patients with ideal healing. If cranioplasty was required, 39%-50% of surgeons counseled against some participation (most commonly restricting football/rugby, boxing, ice hockey, lacrosse, and wrestling), depending on the extent of the cranioplasty. Overall, more plastic surgeons (56%-67%) counseled against sports participation (including lower-contact sports such as baseball/softball, basketball, gymnastics, and soccer) than neurosurgeons (22%-33%) in patients who required cranioplasty., Conclusions: SynRG surgeons generally did not counsel against sports participation (including contact sports) for children with a history of SSC surgery as an infant who had ideal healing. In patients requiring cranioplasty, 39%-50% of surgeons recommended against high-contact sports participation.
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- 2025
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3. Introduction. Ongoing challenges in pediatric craniofacial surgery.
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Kestle JRW, Riva-Cambrin J, Bonfield CM, Lee A, and Strahle JM
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- 2025
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4. Does machine learning improve prediction accuracy of the Endoscopic Third Ventriculostomy Success Score? A contemporary Hydrocephalus Clinical Research Network cohort study.
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Malhotra AK, Kulkarni AV, Verhey LH, Reeder RW, Riva-Cambrin J, Jensen H, Pollack IF, McDowell M, Rocque BG, Tamber MS, McDonald PJ, Krieger MD, Pindrik JA, Isaacs AM, Hauptman JS, Browd SR, Whitehead WE, Jackson EM, Wellons JC 3rd, Hankinson TC, Chu J, Limbrick DD Jr, Strahle JM, and Kestle JRW
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- Humans, Female, Male, Infant, Child, Preschool, Cohort Studies, Child, Treatment Outcome, Neuroendoscopy methods, Machine Learning, Hydrocephalus surgery, Hydrocephalus diagnostic imaging, Ventriculostomy methods, Third Ventricle surgery, Third Ventricle diagnostic imaging
- Abstract
Purpose: This Hydrocephalus Clinical Research Network (HCRN) study had two aims: (1) to compare the predictive performance of the original ETV Success Score (ETVSS) using logistic regression modeling with other newer machine learning models and (2) to assess whether inclusion of imaging variables improves prediction performance using machine learning models., Methods: We identified children undergoing first-time ETV for hydrocephalus that were enrolled prospectively at HCRN sites between 200 and 2020. The primary outcome was ETV success 6 months after index surgery. The cohort was randomly divided into training (70%) and testing (30%) datasets. The classic ETVSS variables were used for logistic regression and machine learning models. Predictive performance of each model was evaluated on the testing dataset using area under the receiver operating characteristic curve (AUROC)., Results: There were 752 patients that underwent first time ETV, of which 185 patients (24.6%) experienced ETV failure within 6 months. For aim 1, using the classic ETVSS variables, machine learning models did not outperform logistic regression with AUROC 0.60 (95% CI: 0.52-0.69) for Naïve Bayes (highest machine learning model performance) and 0.68 (95% CI: 0.60-0.76) for logistic regression. After inclusion of imaging features (aim 2), machine learning model prediction improved but remained no better than the above logistic regression with the highest AUROC of 0.67 (95% CI: 0.59-0.75) attained using Naïve Bayes architecture compared to 0.68 (95% CI: 0.59-0.76) for logistic regression., Conclusions: This contemporary multicenter observational cohort study demonstrated that machine learning modeling strategies did not improve performance of the ETVSS model over logistic regression., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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5. Spinal cord-spinal canal disproportion following treatment for syringomyelia associated with Chiari malformation type I: illustrative case.
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Nair A, Gupta VP, Kolmetzky D, Strahle JM, and Limbrick DD
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Background: Chiari malformation type I (CM-I) is a common pediatric neurosurgical condition that is often associated with syringomyelia (SM) and spine deformity. The association of these three conditions is well recognized, but the pathophysiology linking them has yet to be fully elucidated., Observations: This case report describes the unusual course of a 13-year-old male with CM-I, a large holocord syrinx, and progressive scoliosis who developed an angiography-negative subarachnoid hemorrhage (SAH) 4 months after successful posterior fossa decompression with duraplasty (PFDD). Notably, his cervical spinal canal diameter was increased relative to normative data. After presenting with SAH, he was treated with a course of lumbar cerebrospinal fluid drainage, which relieved his symptoms, and he had no further incidents. His syrinx responded to PFDD with a dramatic decrease in spinal cord diameter, in contradistinction to his dilated bony spinal canal. He is presently 4 years out from his SAH and doing well clinically., Lessons: This report describes the first case of nonaneurysmal SAH following PFDD for CM-I and SM and explores a possible link between SM and bony spinal canal diameter. https://thejns.org/doi/10.3171/CASE24272.
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- 2024
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6. Family Experiences with Diagnosis of Craniosynostosis: Thematic Analysis of Online Discussion Boards.
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Varagur K, Murphy J, Skolnick GB, Naidoo SD, McEvoy SD, Strahle JM, and Patel KB
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- Humans, Female, Parents psychology, Male, Internet, Craniosynostoses psychology, Grounded Theory, Qualitative Research
- Abstract
Objective: Apply thematic analysis of online discussion boards to characterize families' experiences and concerns regarding craniosynostosis diagnoses to aid physicians in tailoring care to families., Design: Grounded theory-based qualitative analysis., Setting: Discussion boards related to craniosynostosis identified via Google and Yahoo., Patients/participants: Posts about craniosynostosis between 2017-2022., Interventions: Thematic analysis was performed using three rounds of coding. Post features including author type and use of technical language were examined., Main Outcome Measure: Overarching themes emerging from analysis of posts, with forums analyzed until sufficient thematic repetition was observed., Results: 366 posts from 4 websites by 290 unique users were included. Parents of patients with craniosynostosis wrote 59% of posts while patients wrote 4%. Five selective codes were identified: 1) Building Community, 2) Diagnosis/Evaluation, 3) Treatment, 4) Outcomes, and 5) Emotional Concerns. Building Community was the most assigned code (85% of posts). 71% of parents' posts expressing emotional concerns expressed negative emotions, commonly regarding anxiety about diagnosis (71%), frustration about doctors' responses (21%), or negative reactions to online search results (17%). 88% of patients' posts expressed positive emotions, discussing positive long-term outcomes. Concerns that may guide physicians included anxiety about delayed diagnosis, difficulty distinguishing postpartum head shape changes from craniosynostosis, and difficulty finding a care team., Conclusions: Online discussion boards allow families of patients with craniosynostosis to share experiences and find community. Improving communication between surgeons, pediatricians, and families about timing of evaluation and revising online information about this condition may ameliorate some anxiety associated with this diagnosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Patel is a Stryker CMF consultant for education and product design. All other authors have no conflicts to declare.
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- 2024
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7. MR Cranial Bone Imaging: Evaluation of Both Motion-Corrected and Automated Deep Learning Pseudo-CT Estimated MR Images.
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Linkugel AD, Wang T, Boroojeni PE, Eldeniz C, Chen Y, Skolnick GB, Commean PK, Merrill CM, Strahle JM, Goyal MS, An H, and Patel KB
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- Humans, Male, Female, Adolescent, Child, Skull Fractures diagnostic imaging, Sensitivity and Specificity, Cranial Sutures diagnostic imaging, Child, Preschool, Motion, Skull diagnostic imaging, Deep Learning, Magnetic Resonance Imaging methods, Tomography, X-Ray Computed methods
- Abstract
Background and Purpose: CT imaging exposes patients to ionizing radiation. MR imaging is radiation free but previously has not been able to produce diagnostic-quality images of bone on a timeline suitable for clinical use. We developed automated motion correction and use deep learning to generate pseudo-CT images from MR images. We aim to evaluate whether motion-corrected pseudo-CT produces cranial images that have potential to be acceptable for clinical use., Materials and Methods: Patients younger than age 18 who underwent CT imaging of the head for either trauma or evaluation of cranial suture patency were recruited. Subjects underwent a 5-minute golden-angle stack-of-stars radial volumetric interpolated breath-hold MR image. Motion correction was applied to the MR imaging followed by a deep learning-based method to generate pseudo-CT images. CT and pseudo-CT images were evaluated and, based on indication for imaging, either presence of skull fracture or cranial suture patency was first recorded while viewing the MR imaging-based pseudo-CT and then recorded while viewing the clinical CT., Results: A total of 12 patients underwent CT and MR imaging to evaluate suture patency, and 60 patients underwent CT and MR imaging for evaluation of head trauma. For cranial suture patency, pseudo-CT had 100% specificity and 100% sensitivity for the identification of suture closure. For identification of skull fractures, pseudo-CT had 100% specificity and 90% sensitivity., Conclusions: Our early results show that automated motion-corrected and deep learning-generated pseudo-CT images of the pediatric skull have potential for clinical use and offer a high level of diagnostic accuracy when compared with standard CT scans., (© 2024 by American Journal of Neuroradiology.)
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- 2024
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8. Mapping the landscape of pediatric neurosurgery: geography, gender, and trends over time.
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Muzyka L, Pugazenthi S, Kann MR, and Strahle JM
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- Humans, Female, United States, Male, Neurosurgeons trends, Leadership, Sex Factors, Fellowships and Scholarships, Physicians, Women trends, Physicians, Women statistics & numerical data, Neurosurgery education, Neurosurgery trends, Pediatrics trends
- Abstract
Objective: Recently there has been an increase in pediatric neurosurgical fellowship graduates. It is important to understand the current pediatric neurosurgical workforce to help with prospective strategic workforce planning. The authors sought to determine 1) the geographic distribution and regional retention after training and 2) academic and leadership metrics by geographic location, era of training, and gender for practicing pediatric neurosurgeons in the United States., Methods: Current practicing pediatric neurosurgeons were identified through American Board of Pediatric Neurological Surgery (ABPNS) certification status and the American Association of Neurological Surgeons directory. NIH RePORTER, Web of Science, and departmental and hospital networking websites were used to collect data on demographics, training, leadership, NIH involvement, and academic metrics., Results: A total of 298 ABPNS-certified pediatric neurosurgeons were identified as currently practicing in the United States. Of these pediatric neurosurgeons, 26.2% were women, 74.5% were academic, and 11.7% have received current or past NIH funding. There were significant differences in the concentration of pediatric neurosurgeons per general population based on region. A total of 117 (39.3%) pediatric neurosurgeons held leadership positions; 4 (1.3%) served as neurosurgery department chairs, 67 (22.5%) served as chief of pediatric neurosurgery (9 of whom were women), 12 (4.0%) served as residency program directors, and 32 (10.7%) served as pediatric fellowship directors. Women were more likely to currently practice in the same region in which they trained for medical school (p = 0.050), have a lower academic rank (p = 0.004), and have a lower h-index (p < 0.001). Pediatric neurosurgeons practicing in the Northeast were more likely to have completed residency (p = 0.022) and medical school (p = 0.002) in the same region as their current practice., Conclusions: There are differences in the concentration of pediatric neurosurgeons based on region. In pediatric neurosurgery, women hold fewer leadership positions, have lower academic ranks, and are less academically impactful as measured by the h-index. As the demand for pediatric neurosurgeons evolves, thoughtful monitoring of the distribution and composition of the neurosurgical workforce can help ensure equitable access to care across the country.
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- 2024
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9. MRI analysis of neurodevelopmental anatomy in myelomeningocele: prenatal vs postnatal repair.
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Bruzek AK, Koller GM, Karuparti S, Varagur K, Dunbar A, Flanders TM, Mingo M, Sudanagunta K, Bligard KH, Odibo A, Vrecenak J, Mian A, and Strahle JM
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- Humans, Female, Pregnancy, Retrospective Studies, Infant, Newborn, Male, Ultrasonography, Prenatal, Adult, Meningomyelocele diagnostic imaging, Meningomyelocele surgery, Meningomyelocele embryology, Meningomyelocele complications, Magnetic Resonance Imaging
- Abstract
Objective: Compared with postnatal repair, prenatal myelomeningocele (MMC) repair is associated with improved motor function and decreased need for cerebrospinal fluid (CSF) diversion. It is unknown how prenatal surgery alters neuroanatomical structures identifiable on magnetic resonance imaging (MRI). The purpose of this study was to use MRI to compare neurodevelopmental anatomy in patients undergoing fetal MMC repair compared with those undergoing postnatal repair., Methods: This was a retrospective review of neonates who underwent prenatal or postnatal MMC repair at our institution between 2016 and 2021. Imaging data, including prenatal ultrasound and pre- and postnatal MRI examinations, if available, were retrieved. We analyzed anatomical findings characteristically seen on MRI of the neuroaxis in patients with MMC and compared imaging findings between patients with prenatal vs postnatal MMC repair., Results: The study population included 61 patients who underwent surgical repair for MMC during the 6-year study period, of whom 25 underwent prenatal repair and 36 postnatal repair. CSF diversion was required in 24% of the prenatally repaired cohort vs 67% of the postnatally repaired cohort (P = 0.001). On postnatal MRI, a syrinx was present in 13% of the prenatally repaired cohort vs 42% in the postnatally repaired cohort (P = 0.02). Postnatal corpus callosal (CC) morphology was abnormal in 54% of the prenatally repaired cohort vs 53% of the postnatally repaired cohort (P = 0.92), while falx morphology was normal in 92% of the prenatally repaired cohort vs 34% of the postnatally repaired cohort (P < 0.001). On postnatal MRI, patients in the prenatally repaired cohort had a shorter tentorium-to-foramen-magnum distance compared with those in the postnatally repaired cohort (mean, 18.43 mm vs 22.42 mm; P = 0.01), a larger foramen magnum diameter (mean, 22.87 mm vs 18.94 mm; P < 0.001) and a smaller degree of hindbrain herniation (mean, 1.53 mm vs 8.72 mm; P < 0.001). The cerebral aqueduct was patent in 79% of the prenatally repaired cohort vs 100% of the postnatally repaired cohort on postnatal MRI (P = 0.008). Between the two cohorts, at postnatal MRI there was no significant difference in the presence of gray-matter heterotopia, presence of the septum pellucidum or size of the massa intermedia., Conclusions: We report variations in developmental neuroanatomy in patients with MMC, including rates of CC dysgenesis, gray-matter heterotopia and additional cranial and spinal MRI findings. Compared to postnatal surgery, prenatal surgery is associated with changes to infratentorial anatomy, with minimal effect on supratentorial brain development. This information will be useful in counseling parents affected by fetal MMC and in understanding how prenatal repair of MMC affects brain development. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)
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- 2024
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10. Indications for cerebral revascularization for moyamoya syndrome in pediatric sickle cell disease determined by Delphi methodology.
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Robert AP, Hanel RA, Adelson PD, Lang SS, Grabb P, Greene S, Johnston JM, Leonard J, Magge SN, Marupudi NI, Piatt J, De Oliveira Sillero R, Smith ER, Smith J, Strahle JM, Vadivelu S, Wellons JC, Wrubel D, Hatem A, Moody C, Han SH, Montaser A, Millican N, Pederson JM, Dain AS, Beslow LA, and Aldana PR
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- Humans, Child, Female, Male, Consensus, Adolescent, Surveys and Questionnaires, Moyamoya Disease surgery, Moyamoya Disease complications, Moyamoya Disease diagnostic imaging, Anemia, Sickle Cell complications, Anemia, Sickle Cell surgery, Cerebral Revascularization methods, Delphi Technique
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Objective: Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US., Methods: Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group's agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses., Results: The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%-70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios., Conclusions: There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.
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- 2024
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11. Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.
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Yang PH, Karuparti S, Varagur K, Alexopoulos D, Reeder RW, Lean RE, Rogers CE, Limbrick DD, Smyser CD, and Strahle JM
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- Humans, Male, Female, Retrospective Studies, Infant, Newborn, Infant, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage complications, Cerebral Hemorrhage pathology, Ventriculostomy, Child, Preschool, Cerebrospinal Fluid Shunts, Neurodevelopmental Disorders etiology, Neurodevelopmental Disorders diagnostic imaging, Cerebral Intraventricular Hemorrhage diagnostic imaging, Hydrocephalus diagnostic imaging, Hydrocephalus surgery, Hydrocephalus etiology
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Objective: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics., Methods: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores., Results: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes., Conclusions: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.
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- 2024
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12. Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.
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Ravindra VM, Riva-Cambrin J, Jensen H, Whitehead WE, Kulkarni AV, Limbrick DD, Wellons JC, Naftel RP, Rozzelle CJ, Rocque BG, Pollack IF, McDowell MM, Tamber MS, Hauptman JS, Browd SR, Pindrik J, Isaacs AM, McDonald PJ, Hankinson TC, Jackson EM, Chu J, Krieger MD, Simon TD, Strahle JM, Holubkov R, Reeder R, and Kestle JRW
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- Humans, Child, Female, Male, Child, Preschool, Adolescent, Infant, Postoperative Complications etiology, Postoperative Complications epidemiology, Ventriculoperitoneal Shunt methods, Treatment Outcome, Retrospective Studies, Heart Atria surgery, Hydrocephalus surgery, Hydrocephalus etiology, Cerebrospinal Fluid Shunts
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Objective: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort., Methods: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months., Results: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013)., Conclusions: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.
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- 2024
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13. A qualitative analysis of patient and caregiver experiences with myelomeningocele through online discussion boards.
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Koneru S, Bhavsar S, Pugazenthi S, Koller GM, Karuparti S, Kann MR, and Strahle JM
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- Humans, Female, Male, Quality of Life psychology, Qualitative Research, Parents psychology, Child, Adult, Internet, Meningomyelocele psychology, Caregivers psychology
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Purpose: Patients and caregivers impacted by myelomeningocele (MMC) use online discussion board forums to create community and share information and concerns about this complex medical condition. We aim to identify the primary concerns expressed on these forums with the goal of understanding gaps in care that may merit investment of resources to improve care received by this population., Methods: Anonymous posts from online MMC discussion boards were compiled using internet search engines. Posts were then analyzed using an adaptation of the Grounded Theory Method, a three-step system involving open, axial, and selective coding of the data by two independent researchers to identify common themes., Results: Analysis of 400 posts written primarily by parents (n = 342, 85.5%) and patients (n = 45, 11.25%) yielded three overarching themes: questions surrounding quality of life, a lack of support for mothers of children with MMC, and confusion with a complex healthcare system. Many posts revealed concerns about management and well-being with MMC, including posts discussing symptoms and related conditions (n = 299, 75.75%), treatments (n = 259, 65.75%), and emotional aspects of MMC (n = 146, 36.5%). Additionally, families, especially mothers, felt a lack of support in their roles as caregivers. Finally, in 118 posts (29.5%), patients and families expressed frustration with navigating a complex healthcare system and finding specialists whose opinions they trusted., Conclusions: MMC is a complex medical condition that impacts patients and families in unique ways. Analysis of online discussion board posts identified key themes to be addressed in order to improve the healthcare experiences of those impacted by MMC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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14. Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.
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Pugazenthi S, Malacon K, Kim NC, Stuebe CM, Yoh N, Bhanja D, Walker E, Bauman MMJ, Becker K, Johnson GW, Caston RM, Lee H, Strahle JM, and Ben-Haim S
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- Humans, Female, Male, Adult, United States, Surveys and Questionnaires, Racial Groups, Sex Factors, Internship and Residency, Young Adult, Students, Medical psychology, Neurosurgery education, Career Choice
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Objective: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race., Methods: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction., Results: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis., Conclusions: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.
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- 2024
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15. Paediatric hydrocephalus.
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Kahle KT, Klinge PM, Koschnitzky JE, Kulkarni AV, MacAulay N, Robinson S, Schiff SJ, and Strahle JM
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- Humans, Child, Infant, Ventriculostomy methods, Cerebrospinal Fluid Shunts methods, Infant, Newborn, Hydrocephalus physiopathology, Hydrocephalus diagnosis, Hydrocephalus therapy, Hydrocephalus etiology, Hydrocephalus complications
- Abstract
Hydrocephalus is classically considered as a failure of cerebrospinal fluid (CSF) homeostasis that results in the active expansion of the cerebral ventricles. Infants with hydrocephalus can present with progressive increases in head circumference whereas older children often present with signs and symptoms of elevated intracranial pressure. Congenital hydrocephalus is present at or near birth and some cases have been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. Acquired hydrocephalus can develop at any time after birth, is often caused by central nervous system infection or haemorrhage and has been associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. Treatments for hydrocephalus mainly include surgical CSF shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization. In utero treatment of fetal hydrocephalus is possible via surgical closure of associated neural tube defects. Long-term outcomes for children with hydrocephalus vary widely and depend on intrinsic (genetic) and extrinsic factors. Advances in genomics, brain imaging and other technologies are beginning to refine the definition of hydrocephalus, increase precision of prognostication and identify nonsurgical treatment strategies., (© 2024. Springer Nature Limited.)
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- 2024
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16. What to do with an incidental finding of a fused sagittal suture: a modified Delphi study.
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Chiang SN, Reckford J, Alexander AL, Birgfeld CB, Bonfield CM, Couture DE, David LR, French B, Gociman B, Goldstein JA, Golinko MS, Kestle JRW, Lee A, Magge SN, Pollack IF, Rottgers SA, Runyan CM, Smyth MD, Wilkinson CC, Skolnick GB, Strahle JM, and Patel KB
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- Humans, Child, Preschool, Female, Male, Infant, Neurosurgeons, Algorithms, Craniosynostoses surgery, Delphi Technique, Incidental Findings, Cranial Sutures surgery
- Abstract
Objective: As many as 5% of normocephalic children may have a prematurely fused sagittal suture, yet the clinical significance and best course of management of this finding remain unclear. Providers in the Synostosis Research Group were surveyed to create a multicenter consensus on an optimal treatment and monitoring algorithm for this condition., Methods: A four-round modified Delphi method was utilized. The first two rounds consisted of anonymous surveys distributed to 10 neurosurgeons and 9 plastic surgeons with expertise in craniosynostosis across 9 institutions, and presented 3 patients (aged 3 years, 2 years, and 2 months) with incidentally discovered fused sagittal sutures, normal cephalic indices, and no parietal dysmorphology. Surgeons were queried about their preferred term for this entity and how best to manage these patients. Results were synthesized to create a treatment algorithm. The third and fourth feedback rounds consisted of open discussion of the algorithm until no further concerns arose., Results: Most surgeons preferred the term "premature fusion of the sagittal suture" (93%). At the conclusion of the final round, all surgeons agreed to not operate on the 3- and 2-year-old patients unless symptoms of intracranial hypertension or papilledema were present. In contrast, 50% preferred to operate on the 2-month-old. However, all agreed to utilize shared decision-making, taking into account any concerns about future head shape and neurodevelopment. Panelists agreed that patients over 18 months of age without signs or symptoms suggesting elevated intracranial pressure (ICP) should not undergo surgical treatment., Conclusions: Through the Delphi method, a consensus regarding management of premature fusion of the sagittal suture was obtained from a panel of North American craniofacial surgeons. Without signs or symptoms of ICP elevation, surgery is not recommended in patients over 18 months of age. However, for children younger than 18 months, surgery should be discussed with caregivers using a shared decision-making process.
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- 2024
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17. The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.
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Yahanda AT, Koueik J, Ackerman LL, Adelson PD, Albert GW, Aldana PR, Alden TD, Anderson RCE, Bauer DF, Bethel-Anderson T, Bierbrauer K, Brockmeyer DL, Chern JJ, Couture DE, Daniels DJ, Dlouhy BJ, Durham SR, Ellenbogen RG, Eskandari R, Fuchs HE, Grant GA, Graupman PC, Greene S, Greenfield JP, Gross NL, Guillaume DJ, Hankinson TC, Heuer GG, Iantosca M, Iskandar BJ, Jackson EM, Jallo GI, Johnston JM, Kaufman BA, Keating RF, Khan NR, Krieger MD, Leonard JR, Maher CO, Mangano FT, Martin J, McComb JG, McEvoy SD, Meehan T, Menezes AH, Muhlbauer MS, O'Neill BR, Olavarria G, Ragheb J, Selden NR, Shah MN, Shannon CN, Shimony JS, Smyth MD, Stone SSD, Strahle JM, Tamber MS, Torner JC, Tuite GF, Tyler-Kabara EC, Wait SD, Wellons JC, Whitehead WE, Park TS, Limbrick DD, and Ahmed R
- Subjects
- Humans, Female, Male, Child, Adolescent, Treatment Outcome, Child, Preschool, Decompression, Surgical methods, Retrospective Studies, Cervical Vertebrae surgery, Cervical Vertebrae abnormalities, Cervical Vertebrae diagnostic imaging, Arnold-Chiari Malformation surgery, Arnold-Chiari Malformation diagnostic imaging, Syringomyelia surgery, Syringomyelia diagnostic imaging, Cervical Atlas abnormalities, Cervical Atlas surgery, Cervical Atlas diagnostic imaging, Occipital Bone surgery, Occipital Bone diagnostic imaging, Occipital Bone abnormalities, Spinal Fusion methods, Atlanto-Occipital Joint diagnostic imaging, Atlanto-Occipital Joint surgery, Atlanto-Occipital Joint abnormalities
- Abstract
Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF)., Methods: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio., Results: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95)., Conclusions: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.
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- 2024
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18. Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.
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Sun LR, Jordan LC, Smith ER, Aldana PR, Kirschen MP, Guilliams K, Gupta N, Steinberg GK, Fox C, Harrar DB, Lee S, Chung MG, Dirks P, Dlamini N, Maher CO, Lehman LL, Hong SJ, Strahle JM, Pineda JA, Beslow LA, Rasmussen L, Mailo J, Piatt J, Lang SS, Adelson PD, Dewan MC, Mineyko A, McClugage S, Vadivelu S, Dowling MM, and Hersh DS
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- Child, Humans, Delphi Technique, Perioperative Care, Postoperative Care, Treatment Outcome, Retrospective Studies, Moyamoya Disease surgery, Stroke etiology, Cerebral Revascularization adverse effects
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Background: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities., Methods: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement., Results: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery., Conclusions: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)
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- 2024
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19. Predictors and timing of hydrocephalus treatment in patients undergoing prenatal versus postnatal surgery for myelomeningocele.
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Karuparti S, Dunbar A, Varagur K, Sudanagunta K, Mingo M, Bligard KH, Odibo A, Vrecenak J, McEvoy S, Limbrick D, Peglar Marsala L, Anadkat J, Mian A, and Strahle JM
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- Humans, Female, Male, Retrospective Studies, Infant, Newborn, Pregnancy, Ultrasonography, Prenatal, Gestational Age, Treatment Outcome, Infant, Hydrocephalus surgery, Hydrocephalus etiology, Hydrocephalus diagnostic imaging, Meningomyelocele surgery, Meningomyelocele complications, Meningomyelocele diagnostic imaging
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Objective: Although hydrocephalus rates have decreased with intrauterine surgery for myelomeningocele (MMC), 40%-85% of children with MMC still go on to develop hydrocephalus. Prenatal ventricle size is known to be associated with later development of hydrocephalus; however, it is not known how prediction measures or timing of hydrocephalus treatment differ between pre- and postnatal surgery for MMC. The goal of this study was to determine anatomical, clinical, and radiological characteristics that are associated with the need for and timing of hydrocephalus treatment in patients with MMC., Methods: The authors retrospectively identified patients from Barnes Jewish Hospital or St. Louis Children's Hospital between 2016 and 2021 who were diagnosed with MMC prenatally and underwent either pre- or postnatal repair. Imaging, clinical, and demographic data were examined longitudinally between treatment groups and hydrocephalus outcomes., Results: Fifty-eight patients were included (27 females, 46.6%), with a mean gestational age at birth of 36.8 weeks. Twenty-three patients (39.7%) underwent prenatal surgery. For the overall cohort, the ventricle size at prenatal ultrasound (HR 1.175, 95% CI 1.071-1.290), frontal-occipital horn ratio (FOHR) at birth > 0.50 (HR 3.603, 95% CI 1.488-8.720), and mean rate of change in head circumference (HC) in the first 90 days after birth (> 0.10 cm/day: HR 12.973, 95% CI 4.262-39.486) were identified as predictors of hydrocephalus treatment. The factors associated with hydrocephalus in the prenatal cohort were FOHR at birth > 0.50 (HR 27.828, 95% CI 2.980-259.846) and the rate of change in HC (> 0.10 cm/day: HR 39.414, 95% CI 2.035-763.262). The factors associated with hydrocephalus in the postnatal cohort were prenatal ventricle size (HR 1.126, 95% CI 1.017-1.246) and the mean rate of change in HC (> 0.10 cm/day: HR 24.202, 95% CI 5.119-114.431). FOHR (r = -0.499, p = 0.008) and birth HC (-0.409, p = 0.028) were correlated with time to hydrocephalus across both cohorts. For patients who underwent treatment for hydrocephalus, those in the prenatal surgery group were significantly more likely to develop hydrocephalus after 3 months than those treated with postnatal surgery, although the overall rate of hydrocephalus was significantly higher in the postnatal surgery group (p = 0.018)., Conclusions: Clinical and imaging factors associated with hydrocephalus treatment differ between those receiving pre- versus postnatal MMC repair, and while the overall rate of hydrocephalus is lower, those undergoing prenatal repair are more likely to develop hydrocephalus after 3 months of age. This has implications for clinical follow-up timing for patients treated prenatally, who may live at a distance from the treatment site.
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- 2024
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20. Head growth in patients with myelomeningocele treated with prenatal and postnatal surgery.
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Karuparti S, Flanders TM, Dunbar A, Varagur K, and Strahle JM
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- Humans, Female, Male, Retrospective Studies, Infant, Newborn, Pregnancy, Infant, Gestational Age, Cephalometry, Meningomyelocele surgery, Meningomyelocele complications, Head surgery, Hydrocephalus surgery
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Objective: The need for permanent CSF diversion is lower in patients who have undergone prenatal surgery for myelomeningocele (MMC) than in those who have undergone postnatal closure. Differences in brain development and head growth between treatment groups are not known, particularly for those who do not require surgical treatment for hydrocephalus. The objective of this study was to determine differences in head growth and to generate MMC-specific head circumference (HC) growth curves for patients who underwent either prenatal or postnatal surgery., Methods: The authors retrospectively identified patients from St. Louis Children's Hospital who were treated for MMC between 2016 and 2021. HC data were obtained from birth until the most recent follow-up or hydrocephalus treatment. Nonlinear least-squares regression analysis was performed to fit the data into four models: two-term power, Gompertz, West ontogenetic, and Weibull. Subsequently, the curves were assessed for their utility in predicting hydrocephalus treatment., Results: Sixty-one patients (29 females [47.5%], 25 [41%] underwent prenatal surgery, mean gestational age at birth 36.6 weeks) were included in the study. The Weibull model best fit the HC data (prenatal adjusted R2 = 0.95, postnatal adjusted R2 = 0.95), while the Gompertz model had the worst fit (prenatal adjusted R2 = 0.56, postnatal adjusted R2 = 0.39) across both cohorts. Prenatal MMC repair patients had significantly larger HC measurements than their postnatal repair counterparts. The 50th percentile of the Weibull curve was determined as a useful threshold for hydrocephalus treatment: children with HC measurements that crossed and remained above this threshold were significantly more likely to have hydrocephalus treatment regardless of time of MMC repair (prenatal relative risk [RR] 10.0 [95% CI 1.424-70.220], sensitivity 85.7% [95% CI 0.499-0.984], and specificity 82.4% [95% CI 0.600-0.948]; postnatal RR 4.750 [95% CI 1.341-16.822], sensitivity 90.5% [95% CI 0.728-0.980], and specificity 75.0% [95% CI 0.471-0.924]). The HC growth curves of the MMC patients treated prenatally were significantly larger than the WHO HC curves (p < 0.001)., Conclusions: The Weibull model was identified as the HC growth curve with the best fit for MMC patients and serves as a useful predictor of hydrocephalus treatment. For MMC patients with hydrocephalus, prenatal repair patients fit the model well but postnatal repair patients did not, potentially indicating different mechanisms of hydrocephalus development. Those treated prenatally had significantly larger HC measurements compared with both the general population and those treated postnatally. Further study is needed to understand the long-term cognitive outcomes and optimal management of clinically asymptomatic patients with large HC measurements who were treated prenatally for MMC.
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- 2024
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21. The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact.
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Hale AT, Boudreau H, Devulapalli R, Duy PQ, Atchley TJ, Dewan MC, Goolam M, Fieggen G, Spader HL, Smith AA, Blount JP, Johnston JM, Rocque BG, Rozzelle CJ, Chong Z, Strahle JM, Schiff SJ, and Kahle KT
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- Humans, Cerebral Hemorrhage, Choroid Plexus, Hydrodynamics, Hydrocephalus genetics, Intracranial Hypertension
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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., (© 2024. The Author(s).)
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- 2024
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22. Cognitive Development in Lambdoid Craniosynostosis: A Systematic Review and Meta-Analysis.
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Chiang SN, Fotouhi AR, Doering MM, Skolnick GB, Naidoo SD, Strahle JM, McEvoy SD, and Patel KB
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- Humans, Craniosynostoses psychology, Child Development, Infant, Cognition
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Objective: Lambdoid craniosynostosis affects approximately 1 in 33 000 live births per year, and surgical correction is often sought in order to achieve normocephaly and allow for adequate brain growth. However, the effects of lambdoid synostosis and its treatment on cognitive development are unknown., Design: Systematic review and meta-analysis., Patients, Participants: A systematic review of Ovid Medline, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov was conducted in January 2022. Included studies assessed cognitive development of patients with nonsyndromic unilateral lambdoid craniosynostosis., Main Outcome Measures: Results of developmental tests were compared to normative data or controls to generate Hedges' g for meta-analysis., Results: Nine studies met the inclusion criteria. Meta-analysis of 3 studies describing general cognition showed that cases scored significantly lower than their peers, but within 1 standard deviation ( g = 0.37, 95% CI [-0.64, -0.10], P = .01). Meta-analysis of verbal and psychomotor development showed no significant differences in children with lambdoid synostosis. Studies were of fair quality and had moderate-to-high heterogeneity., Conclusions: Patients with lambdoid craniosynostosis may score slightly below average on tests of general cognition in comparison to normal controls, but results in other domains are variable. Analyses were limited by small sample sizes. Multidisciplinary care and involvement of a child psychologist may be helpful in identifying areas of concern and providing adequate scholastic support. Further research recruiting larger cohorts will be necessary to confirm these findings and extend them to other developmental domains such as attention and executive function., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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23. Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.
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Garcia-Bonilla M, Yahanda AT, Isaacs AM, Baksh B, Akbari SHA, Botteron H, Morales DM, Han RH, McAllister Ii JP, Mathur AM, Strahle JM, Smyser CD, and Limbrick DD Jr
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- Infant, Infant, Newborn, Humans, Infant, Premature, Clinical Relevance, Cerebral Hemorrhage complications, Cerebrospinal Fluid, Hydrocephalus cerebrospinal fluid, Central Nervous System Infections complications, Meningitis complications
- Abstract
Background: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters., Methods: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH
1/2 ), 13 IVH grade 3/4 (IVH3/4 ), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age., Results: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2 , BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4 , PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2 . CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4 ., Conclusions: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis., (© 2024. The Author(s).)- Published
- 2024
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24. A re-evaluation of the Endoscopic Third Ventriculostomy Success Score: a Hydrocephalus Clinical Research Network study.
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Verhey LH, Kulkarni AV, Reeder RW, Riva-Cambrin J, Jensen H, Pollack IF, Rocque BG, Tamber MS, McDonald PJ, Krieger MD, Pindrik JA, Hauptman JS, Browd SR, Whitehead WE, Jackson EM, Wellons JC, Hankinson TC, Chu J, Limbrick DD, Strahle JM, and Kestle JRW
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- Humans, Female, Male, Child, Child, Preschool, Prospective Studies, Infant, Treatment Outcome, Adolescent, Neuroendoscopy methods, Follow-Up Studies, Ventriculostomy methods, Hydrocephalus surgery, Hydrocephalus diagnostic imaging, Third Ventricle surgery, Third Ventricle diagnostic imaging
- Abstract
Objective: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities., Methods: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics., Results: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance., Conclusions: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.
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- 2024
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25. Patient and caregiver perceptions of Chiari malformation: a qualitative analysis of online discussion boards.
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Koller GM, Kann MR, Pugazenthi S, Koneru S, Bhavsar S, and Strahle JM
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- Humans, Headache, Caregivers, Arnold-Chiari Malformation surgery
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Objective: Patients and their caregivers utilize online discussion board forums as a means to seek and exchange information about their or a loved one's condition. It is important for providers to be aware of such concerns and experiences. The goal of this study was to identify the primary concerns expressed on these discussion boards regarding Chiari malformation type I (CM) and to help guide clinicians in understanding patient challenges in the treatment of CM., Methods: The authors performed thematic analysis of anonymous online discussion board posts as identified through internet search engines. They then adopted a previously developed grounded theory method that utilizes a three-tiered coding and grouping process of posts based on commonly discovered content themes., Results: Analysis of 400 discussion board posts identified four distinct themes raised by CM patients and their caregivers: the path to diagnosis, symptoms experienced, surgical intervention, and high emotional burden. Although each individual experience was unique, the path toward a CM diagnosis was expressed as a journey involving multiple physicians, alternative diagnoses, and feelings of dismissal from providers. The most common reported symptoms included dizziness, headaches, neck and back pain, sensory issues, weakness and paresthesias of the extremities, speech issues, and general fatigue. Additionally, there was an overall sense of uncertainty from patients seeking advice regarding surgical intervention, with users expressing diverse sentiments that included both positive and negative outcomes regarding surgical treatment. Lastly, a wide range of emotions was expressed related to a CM diagnosis, including concern, worry, anxiety, depression, stress, fear, and frustration., Conclusions: CM is a frequent imaging diagnosis identified in patients presenting with a wide range of symptoms, and as a result this leads to a diverse set of patient experiences. Analysis of CM patient and caregiver discussion boards revealed key themes that clinicians may address when counseling for CM.
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- 2024
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26. A Systematic Review of the State of Neurosurgical Disparities Research: Past, Present, and Future.
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Pugazenthi S, Barpujari A, Patel S, Estes EM, Reddy V, Rogers JL, Hardi A, Lee H, and Strahle JM
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- Humans, Biomedical Research trends, Neurosurgery, Social Determinants of Health, United States, Healthcare Disparities trends, Neurosurgical Procedures trends
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Background: The social determinants of health, which influence healthcare access, patient outcomes, and population-level burden of disease, contribute to health disparities experienced by marginalized patient populations. In the present study, we sought to evaluate the landscape of health disparities research within neurosurgery., Methods: Embase, Ovid-MEDLINE, Scopus, Web of Science, Cochrane Library, and ProQuest Dissertations databases were queried for original research on health disparities regarding access to, outcomes of, and/or postoperative management after neurosurgical procedures in the United States., Results: Of 883 studies screened, 196 were included, of which 144 had a neurosurgery-affiliated author. We found a significant increase in the number of neurosurgical disparities reports beginning in 2010, with only 10 studies reported before 2010. Of the included studies, 3.1% used prospective methods and 63.8% used data from national registries. The disparities analyzed were racial/ethnic (79.6%), economic/socioeconomic (53.6%), gender (18.9%), and disabled populations (0.5%), with 40.1% analyzing multiple or intersecting disparities. Of the included reports, 96.9% were in phase 1 (detecting phase of disparities research), with a few studies in phase 2 (understanding phase), and none in phase 3 (reducing phase). The spine was the most prevalent subspecialty evaluated (34.2%), followed by neuro-oncology (19.9%), cerebrovascular (16.3%), pediatrics (10.7%), functional (9.2%), general neurosurgery (5.1%), and trauma (4.1%). Senior authors with a neurosurgical affiliation accounted for 79.2% of the reports, 93% of whom were academically affiliated., Conclusions: Although a recent increase has occurred in neurosurgical disparities research within the past decade, most studies were limited to the detection of disparities without understanding or evaluating any interventions for a reduction in disparities. Future research in neurosurgical disparities should incorporate the latter 2 factors to reduce disparities and improve outcomes for all patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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27. Iron homeostasis and post-hemorrhagic hydrocephalus: a review.
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Pan S, Hale AT, Lemieux ME, Raval DK, Garton TP, Sadler B, Mahaney KB, and Strahle JM
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Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JW declared a shared parent affiliation with the author TG to the handling editor at the time of review., (Copyright © 2024 Pan, Hale, Lemieux, Raval, Garton, Sadler, Mahaney and Strahle.)
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- 2024
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28. Helmet Therapy for the Management of Deformational Plagiocephaly in Pediatric Patients with Shunted Hydrocephalus.
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Johnson EA, Koller GM, Jafrani R, Patel K, Naidoo S, and Strahle JM
- Abstract
Objective: To evaluate the safety and efficacy of helmet therapy for deformational plagiocephaly in patients with shunted hydrocephalus., Design: Retrospective chart review., Setting: Institutional, tertiary-care hospital., Patients: All patients at St. Louis Children's Hospital between 2014 and 2021 with shunted hydrocephalus who underwent helmet therapy for deformational plagiocephaly., Interventions: Helmet therapy., Main Outcome Measures: Cranial vault asymmetry (CVA), cranial vault asymmetry index (CVAI), and cephalic index (CI) were measured before and after completion of helmet therapy., Results: There were 37 patients with shunted hydrocephalus and documented deformational plagiocephaly. Twelve were managed with helmet therapy. Average age at helmeting initiation and time between shunt placement and helmeting initiation was 5.8 and 4.6 months, respectively. Average CVA, CVAI, and CI at helmeting initiation and termination was 11.6, 7.98, and 85.2, and 6.95, 4.49, and 83.7, respectively. Average duration of helmeting was 3.7 months. CVA and CVAI were significantly lower after helmeting ( P = .0028 and .0021) and 11/12 patients had overall improvement in plagiocephaly., Conclusions: Helmet therapy appears to be a safe and efficacious management strategy for deformational plagiocephaly in patients with shunted hydrocephalus. Despite the occasional need for additional fittings and surveillance beyond the normal schedule, in all cases appropriately fitting helmets were achieved and no major adverse events occurred. This cohort represents a proof of principle for the safety and efficacy of helmet therapy in patients with shunted hydrocephalus. Further work in larger prospective cohorts is needed to confirm these initial findings., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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29. Postnatal meningeal CSF transport is primarily mediated by the arachnoid and pia maters and is not altered after intraventricular hemorrhage-posthemorrhagic hydrocephalus.
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Pan S, Koleske JP, Koller GM, Halupnik GL, Alli AO, Koneru S, DeFreitas D, Ramagiri S, and Strahle JM
- Subjects
- Animals, Rats, Pia Mater, Gold, Meninges, Arachnoid, Cerebral Hemorrhage, Metal Nanoparticles, Hydrocephalus
- Abstract
Background: CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine, is less understood. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to meningeal CSF solute distribution in a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF solute interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles., Methods: 1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 min post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 h post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also evaluated., Results: There was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH., Conclusions: Differential CSF tracer handling by the meninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border., (© 2024. The Author(s).)
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- 2024
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30. Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance.
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Ramagiri S, Pan S, DeFreitas D, Yang PH, Raval DK, Wozniak DF, Esakky P, and Strahle JM
- Subjects
- Infant, Newborn, Humans, Animals, Choroid Plexus metabolism, Choroid Plexus pathology, Iron, Deferoxamine therapeutic use, Infant, Premature, Cerebral Hemorrhage metabolism, Hemoglobins metabolism, Hydrocephalus etiology, Hydrocephalus prevention & control, Hydrocephalus pathology, Aquaporins metabolism
- Abstract
Posthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronic hydrocephalus, pathologic choroid plexus iron accumulation, and subsequent choroid plexus injury at post-natal days 5, 7, and 15. This model also results in increased expression of aquaporin-1, Na
+ /K+ /Cl- cotransporter 1, and Na+ /K+ /ATPase on the apical surface of the choroid plexus 24 h post-intraventricular hemorrhage. We use this model to evaluate a clinically relevant treatment strategy for the prevention of neurological sequelae after intraventricular hemorrhage using intraventricular administration of the iron chelator deferoxamine at the time of hemorrhage. Deferoxamine treatment prevented posthemorrhagic hydrocephalus for up to 11 days after intraventricular hemorrhage and prevented the development of sensorimotor gating deficits. In addition, deferoxamine treatment facilitated acute iron clearance through the choroid plexus and subsequently reduced choroid plexus iron levels at 24 h with reversal of hemoglobin-induced aquaporin-1 upregulation on the apical surface of the choroid plexus. Intraventricular administration of deferoxamine at the time of intraventricular hemorrhage may be a clinically relevant treatment strategy for preventing posthemorrhagic hydrocephalus and likely acts through promoting iron clearance through the choroid plexus to prevent hemoglobin-induced injury., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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31. Meningeal CSF transport is primarily mediated by the arachnoid and pia maters during development.
- Author
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Pan S, Koleske J, Koller GM, Halupnik GL, Alli AO, Koneru S, DeFreitas D, Ramagiri U, and Strahle JM
- Abstract
Background: The recent characterization of the glymphatic system and meningeal lymphatics has re-emphasized the role of the meninges in facilitating CSF transport and clearance. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles., Methods: 1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 minutes post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 hours post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also performed., Results: There was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the dura mater of the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH., Conclusions: Differential CSF tracer handling by the leptomeninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border.
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- 2023
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32. Cognition and Brain System Segregation in Pediatric Brain Tumor Patients Treated with Proton Therapy.
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Dowling AV, Seitzman BA, Mitchell TJ, Olufawo M, Dierker DL, Anandarajah H, Dworetsky A, McMichael A, Jiang C, Barbour DL, Schlaggar BL, Limbrick DD, Strahle JM, Rubin JB, Shimony JS, and Perkins SM
- Abstract
Purpose: Pediatric brain tumor patients often experience significant cognitive sequelae. Resting-state functional MRI (rsfMRI) provides a measure of brain network organization, and we hypothesize that pediatric brain tumor patients treated with proton therapy will demonstrate abnormal brain network architecture related to cognitive outcome and radiation dosimetry., Participants and Methods: Pediatric brain tumor patients treated with proton therapy were enrolled on a prospective study of cognitive assessment using the NIH Toolbox Cognitive Domain. rsfMRI was obtained in participants able to complete unsedated MRI. Brain system segregation (BSS), a measure of brain network architecture, was calculated for the whole brain, the high-level cognition association systems, and the sensory-motor systems., Results: Twenty-six participants were enrolled in the study for cognitive assessment, and 18 completed rsfMRI. There were baseline cognitive deficits in attention and inhibition and processing speed prior to radiation with worsening performance over time in multiple domains. Average BSS across the whole brain was significantly decreased in participants compared with healthy controls (1.089 and 1.101, respectively; P = 0.001). Average segregation of association systems was significantly lower in participants than in controls ( P < 0.001) while there was no difference in the sensory motor networks ( P = 0.70). Right hippocampus dose was associated with worse attention and inhibition ( P < 0.05) and decreased segregation in the dorsal attention network ( P < 0.05)., Conclusion: Higher mean dose to the right hippocampus correlated with worse dorsal attention network segregation and worse attention and inhibition cognitive performance. Patients demonstrated alterations in brain network organization of association systems measured with rsfMRI; however, somatosensory system segregation was no different from healthy children. Further work with preradiation rsfMRI is needed to assess the effects of surgery and presence of a tumor on brain network architecture., Competing Interests: Conflicts of Interest: Stephanie Perkins is a paid member of the advisory committee for Mevion Medical Systems, LLC. The authors have no additional conflicts of interest to disclose., (©Copyright 2023 The Author(s).)
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- 2023
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33. The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes.
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Horani A, Gupta DK, Xu J, Xu H, Carmen Puga-Molina LD, Santi CM, Ramagiri S, Brennan SK, Pan J, Koenitzer JR, Huang T, Hyland RM, Gunsten SP, Tzeng SC, Strahle JM, Mill P, Mahjoub MR, Dutcher SK, and Brody SL
- Subjects
- Animals, Humans, Proteomics, Mutation, Phenotype, Proteins genetics, Gene Dosage, Kartagener Syndrome genetics
- Abstract
DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partially preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in DNAAF5 variants. Transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. These findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies.
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- 2023
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34. Impact of neighborhood deprivation and social vulnerability on long-term outcomes and desire for revision in patients with craniosynostosis.
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Varagur K, Murphy J, Ochoa E, Skolnick GB, Naidoo SD, McEvoy SD, Strahle JM, and Patel KB
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- Humans, Cognition, Insurance Coverage, Parents, Retrospective Studies, Social Vulnerability, Craniosynostoses surgery
- Abstract
Objective: The authors utilized the area deprivation index (ADI), a validated composite measure of socioeconomic disadvantage, and the social vulnerability index (SVI) to examine whether differences in neighborhood deprivation impact interventions and outcomes among patients with craniosynostosis., Methods: Patients who underwent craniosynostosis repair between 2012 and 2017 were included. The authors collected data about demographic characteristics, comorbidities, follow-up visits, interventions, complications, desire for revision, and speech, developmental, and behavioral outcomes. National percentiles for ADI and SVI were determined using zip and Federal Information Processing Standard (FIPS) codes. ADI and SVI were analyzed by tertile. Firth logistic regressions and Spearman correlations were used to assess associations between ADI/SVI tertile and outcomes/interventions that differed on univariate analysis. Subgroup analysis was performed to examine these associations in patients with nonsyndromic craniosynostosis. Differences in length of follow-up among the nonsyndromic patients in the different deprivation groups were assessed with multivariate Cox regressions., Results: In total, 195 patients were included, with 37% of patients in the most disadvantaged ADI tertile and 20% of patients in the most vulnerable SVI tertile. Patients in more disadvantaged ADI tertiles were less likely to have physician-reported desire (OR 0.17, 95% CI 0.04-0.61, p < 0.01) or parent-reported desire (OR 0.16, 95% CI 0.04-0.52, p < 0.01) for revision, independent of sex and insurance status. In the nonsyndromic subgroup, inclusion in a more disadvantaged ADI tertile was associated with increased odds of speech/language concerns (OR 4.42, 95% CI 1.41-22.62, p < 0.01). There were no differences in interventions received or outcomes among SVI tertiles (p ≥ 0.24). Neither ADI nor SVI tertile was associated with risk of loss to follow-up among nonsyndromic patients (p ≥ 0.38)., Conclusions: Patients from the most disadvantaged neighborhoods may be at risk for poor speech outcomes and different standards of assessment for revision. Neighborhood measures of disadvantage represent a valuable tool to improve patient-centered care by allowing for modification of treatment protocols to meet the unique needs of patients and their families.
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- 2023
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35. Medical student specialty decision-making and perceptions of neurosurgery. Part 1: Role of gender.
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Pugazenthi S, Johnson GW, Lee H, and Strahle JM
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- Pregnancy, Humans, Male, Female, Career Choice, Neurosurgeons, Surveys and Questionnaires, Neurosurgery education, Students, Medical, Internship and Residency
- Abstract
Objective: Although women account for 50% of medical school graduates, less than 30% of neurosurgery residency applicants and less than 10% of neurosurgeons are female. In order to diversify the field of neurosurgery and recruit more women, it is necessary to understand why there is a disproportionately low entry rate into neurosurgery by female medical students. Factors contributing to specialty decision-making and perceptions of neurosurgery among medical students and residents, specifically differences by gender, have not been studied. The authors aimed to investigate these differences using quantitative and qualitative methods., Methods: A Qualtrics survey was administered at the authors' institution to all medical students and resident physicians to assess factors influencing medical specialty decision-making and perceptions of neurosurgery. Likert scale responses converted to numerical values on a 5-point scale were analyzed with the Mann-Whitney U-test. The chi-square test was performed on binary responses. Semistructured interviews were conducted in a subset of survey respondents and were analyzed by using the grounded theory method., Results: Of the 272 survey respondents, 48.2% were medical students and 61.0% were female. When making specialty decisions, female medical students considered maternity/paternity leave more (p = 0.028) than their male counterparts. Female medical students were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.031) and the technical skill required (p = 0.020) than male medical students. Across both genders, the majority of medical students were hesitant toward neurosurgery due to opportunities for work/life integration (93%), length of training (88%), malignancy of the field (76%), and perceived happiness of the people in the field (76%). Female residents indicated they were more likely than male residents to consider the perceived happiness of the people in the field (p = 0.003), shadowing experiences (p = 0.019), and elective rotations (p = 0.004) when making specialty decisions. Two major themes emerged from the semistructured interviews: 1) maternity needs were more of a concern for women and 2) length of training was a concern for many individuals., Conclusions: Compared with their male counterparts, female students and residents consider different factors and experiences when choosing a medical specialty and have different perceptions of neurosurgery. Exposure to and education within neurosurgery, specifically maternity needs, may help address hesitancy in pursuing a neurosurgical career among female medical students. However, cultural and structural factors may need to be addressed within neurosurgery in order to ultimately increase representation of women.
- Published
- 2023
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36. Medical student specialty decision-making and perceptions of neurosurgery. Part 2: Role of race/ethnicity.
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Pugazenthi S, Johnson GW, Lee H, and Strahle JM
- Subjects
- Humans, United States, Ethnicity, Minority Groups education, Surveys and Questionnaires, Students, Medical, Neurosurgery education, Internship and Residency
- Abstract
Objective: Although individuals underrepresented in medicine (URM) make up 33% of the United States population, only 12.6% of medical school graduates identify as URM; the same percentage of URM students comprises neurosurgery residency applicants. More information is needed to understand how URM students are making specialty decisions and their perceptions of neurosurgery. The authors aimed to evaluate the differences between URM and non-URM medical students and residents in terms of the factors that contribute to specialty decision-making and perceptions of neurosurgery., Methods: A survey was administered to all medical students and resident physicians at a single Midwestern institution to assess factors influencing medical student specialty decision-making and perceptions of neurosurgery. Likert scale responses converted to numerical values on a 5-point scale (strongly agree was the high score of 5) were analyzed with the Mann-Whitney U-test. The chi-square test was performed on the binary responses to examine associations between categorical variables. Semistructured interviews were conducted and analyzed using the grounded theory method., Results: Of 272 respondents, 49.2% were medical students, 51.8% were residents, and 11.0% identified as URM. URM medical students considered research opportunities more than non-URM medical students in specialty decision-making (p = 0.023). When specialty decision-making factors were assessed, URM residents less strongly considered the technical skill required (p = 0.023), their perceived fit in the field (p < 0.001), and seeing people like them in the field (p = 0.010) than their non-URM counterparts when making specialty decisions. Within both medical student and resident respondent cohorts, the authors found no significant differences between URM and non-URM respondents in terms of their specialty decision-making being affected by medical school experiences such as shadowing, elective rotations, family exposure, or having a mentor in the field. URM residents were more concerned about the opportunity to work on health equity issues in neurosurgery than non-URM residents (p = 0.005). The predominant theme that emerged from interviews was the need for more intentional efforts to recruit and retain URM individuals in medicine and specifically neurosurgery., Conclusions: URM students may make specialty decisions differently than non-URM students. URM students were more hesitant toward neurosurgery due to their perceived lack of opportunity for health equity work in neurosurgery. These findings further inform optimization of both new and existing initiatives to improve URM student recruitment and retention in neurosurgery.
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- 2023
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37. Building consensus for the medical management of children with moderate and severe acute spinal cord injury: a modified Delphi study.
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CreveCoeur TS, Alexiades NG, Bonfield CM, Brockmeyer DL, Browd SR, Chu J, Figaji AA, Groves ML, Hankinson TC, Harter DH, Hwang SW, Jea A, Kernie SG, Leonard JR, Martin JE, Oetgen ME, Powers AK, Rozzelle CJ, Skaggs DL, Strahle JM, Wellons JC, Vitale MG, and Anderson RCE
- Abstract
Objective: The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs., Methods: An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements., Results: Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines., Conclusions: General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.
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- 2023
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38. Introduction. Stability and motion: addressing the pathology of Chiari malformation and craniocervical junction.
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Limbrick DD, Brockmeyer DL, Goel A, and Strahle JM
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- Humans, Motion, Arnold-Chiari Malformation
- Published
- 2023
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39. Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain.
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Pan S, Yang PH, DeFreitas D, Ramagiri S, Bayguinov PO, Hacker CD, Snyder AZ, Wilborn J, Huang H, Koller GM, Raval DK, Halupnik GL, Sviben S, Achilefu S, Tang R, Haller G, Quirk JD, Fitzpatrick JAJ, Esakky P, and Strahle JM
- Subjects
- Animals, Gold metabolism, Rodentia, X-Ray Microtomography, Brain metabolism, Cerebrospinal Fluid metabolism, Metal Nanoparticles, Hydrocephalus
- Abstract
Cerebrospinal fluid (CSF) is essential for the development and function of the central nervous system (CNS). However, the brain and its interstitium have largely been thought of as a single entity through which CSF circulates, and it is not known whether specific cell populations within the CNS preferentially interact with the CSF. Here, we develop a technique for CSF tracking, gold nanoparticle-enhanced X-ray microtomography, to achieve micrometer-scale resolution visualization of CSF circulation patterns during development. Using this method and subsequent histological analysis in rodents, we identify previously uncharacterized CSF pathways from the subarachnoid space (particularly the basal cisterns) that mediate CSF-parenchymal interactions involving 24 functional-anatomic cell groupings in the brain and spinal cord. CSF distribution to these areas is largely restricted to early development and is altered in posthemorrhagic hydrocephalus. Our study also presents particle size-dependent CSF circulation patterns through the CNS including interaction between neurons and small CSF tracers, but not large CSF tracers. These findings have implications for understanding the biological basis of normal brain development and the pathogenesis of a broad range of disease states, including hydrocephalus., (© 2023. The Author(s).)
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- 2023
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40. Role of Chiari Decompression in Managing Spinal Deformity Associated with Chiari I Malformation and Syringomyelia.
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Chotai S, Aum DJ, and Strahle JM
- Subjects
- Humans, Decompression, Surgical methods, Treatment Outcome, Retrospective Studies, Syringomyelia complications, Syringomyelia surgery, Scoliosis complications, Scoliosis surgery, Arnold-Chiari Malformation complications, Arnold-Chiari Malformation surgery
- Abstract
CM-I-associated syringomyelia is a risk factor for scoliosis where a larger syrinx size is more likely to be associated with scoliosis. Therefore, the effect of syrinx on scoliosis progression may be alleviated by PFD. There is no difference in the need for fusion surgery between patients undergoing PFD with duraplasty vs. those undergoing extradural decompression; however, PFD with duraplasty is associated with an improvement in curve magnitude compared to extradural decompression alone. Further study on the comparison of PFD techniques for this cohort of patients is needed. PFD is a durable surgical option for patients with CM-I, syrinx, and scoliosis. Early decompression of CM-I in younger patients and those with smaller scoliosis curves at presentation is recommended as there is a higher likelihood of halting curve progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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41. Developing consensus for the management of pediatric cervical spine disorders and stabilization: a modified Delphi study.
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Dastagirzada YM, Alexiades NG, Kurland DB, Anderson SN, Brockmeyer DL, Bumpass DB, Chatterjee S, Groves ML, Hankinson TC, Harter D, Hedequist D, Jea A, Leonard JR, Martin JE, Oetgen ME, Pahys J, Rozzelle C, Strahle JM, Thompson D, Yaszay B, and Anderson RCE
- Subjects
- Child, Humans, Delphi Technique, Postoperative Care, Consensus, Cervical Vertebrae diagnostic imaging, Cervical Vertebrae surgery, Neurosurgical Procedures
- Abstract
Objective: Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery., Methods: A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree)., Results: Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6-12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1-2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level., Conclusions: In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.
- Published
- 2022
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42. Neurodevelopment in unilateral coronal craniosynostosis: a systematic review and meta-analysis.
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Fotouhi AR, Chiang SN, Peterson AM, Doering MM, Skolnick GB, Naidoo SD, Strahle JM, McEvoy SD, and Patel KB
- Subjects
- United States, Humans, Outcome Assessment, Health Care, Databases, Factual, Craniosynostoses surgery
- Abstract
Objective: The current literature on unilateral coronal craniosynostosis is replete with repair techniques and surgical outcomes; however, information regarding neurodevelopment remains unclear. Therefore, the aim of this systematic review and meta-analysis was to comprehensively assess the neurodevelopmental outcomes of patients with unicoronal craniosynostosis compared with their healthy peers or normative data., Methods: A systematic review of the Ovid MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases from database inception to January 19, 2022, was performed. Included studies assessed neurodevelopment of patients with unicoronal craniosynostosis. Two independent reviewers selected studies and extracted data based on a priori inclusion and exclusion criteria. Results of developmental tests were compared with normative data or controls to generate Hedges' g statistics for meta-analysis. The quality of included studies was evaluated using the National Institutes of Health Assessment Tool., Results: A total of 19 studies were included and analyzed, with an overall fair reporting quality. A meta-analysis of 325 postoperative patients demonstrated that scores of general neurodevelopment were below average but within one standard deviation of the norm (Hedges' g = -0.68 [95% CI -0.90 to -0.45], p < 0.001). Similarly, postoperative patients exhibited lower scores in verbal, psychomotor, and mathematic outcome assessments., Conclusions: This systematic review and meta-analysis found that patients with unicoronal craniosynostosis had poorer neurodevelopment, although scores generally remained within the normal range. These data may guide implementation of regular neurocognitive assessments and early learning support of patients with unicoronal craniosynostosis.
- Published
- 2022
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43. Modeling Neonatal Intraventricular Hemorrhage through Intraventricular Injection of Hemoglobin.
- Author
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Miller BA, Pan S, Yang PH, Wang C, Trout AL, DeFreitas D, Ramagiri S, Olson SD, and Strahle JM
- Subjects
- Animals, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage etiology, Hemoglobins, Injections, Intraventricular, Rats, Brain Injuries complications, Hydrocephalus etiology, Hydrocephalus pathology
- Abstract
Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and lifelong neurological deficits. While PHH can be treated by temporary and permanent cerebrospinal fluid (CSF) diversion procedures (ventricular reservoir and ventriculoperitoneal shunt, respectively), there are no pharmacological strategies to prevent or treat IVH-induced brain injury and hydrocephalus. Animal models are needed to better understand the pathophysiology of IVH and test pharmacological treatments. While there are existing models of neonatal IVH, those that reliably result in hydrocephalus are often limited by the necessity for large-volume injections, which may complicate modeling of the pathology or introduce variability in the clinical phenotype observed. Recent clinical studies have implicated hemoglobin and ferritin in causing ventricular enlargement after IVH. Here, we develop a straightforward animal model that mimics the clinical phenotype of PHH utilizing small-volume intraventricular injections of the blood breakdown product hemoglobin. In addition to reliably inducing ventricular enlargement and hydrocephalus, this model results in white matter injury, inflammation, and immune cell infiltration in periventricular and white matter regions. This paper describes this clinically relevant, simple method for modeling IVH-PHH in neonatal rats using intraventricular injection and presents methods for quantifying ventricle size post injection.
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- 2022
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44. Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.
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Yang PH, Almgren-Bell A, Gu H, Dowling AV, Pugazenthi S, Mackey K, Dupépé EB, and Strahle JM
- Abstract
Objective: Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology., Methods: After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted., Results: TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery., Conclusions: CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.
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- 2022
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45. Elevated cerebrospinal fluid iron and ferritin associated with early severe ventriculomegaly in preterm posthemorrhagic hydrocephalus.
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Mahaney KB, Buddhala C, Paturu M, Morales DM, Smyser CD, Limbrick DD, Gummidipundi SE, Han SS, and Strahle JM
- Subjects
- Bilirubin, Cerebral Hemorrhage complications, Cerebral Hemorrhage diagnostic imaging, Cerebral Ventricles diagnostic imaging, Ferritins, Humans, Infant, Newborn, Infant, Premature, Iron, Hydrocephalus cerebrospinal fluid, Hydrocephalus diagnostic imaging, Hydrocephalus etiology, Infant, Premature, Diseases diagnostic imaging, Infant, Premature, Diseases etiology
- Abstract
Objective: Posthemorrhagic hydrocephalus (PHH) following preterm intraventricular hemorrhage (IVH) is among the most severe sequelae of extreme prematurity and a significant contributor to preterm morbidity and mortality. The authors have previously shown hemoglobin and ferritin to be elevated in the lumbar puncture cerebrospinal fluid (CSF) of neonates with PHH. Herein, they evaluated CSF from serial ventricular taps to determine whether neonates with PHH following severe initial ventriculomegaly had higher initial levels and prolonged clearance of CSF hemoglobin and hemoglobin degradation products compared to those in neonates with PHH following moderate initial ventriculomegaly., Methods: In this observational cohort study, CSF samples were obtained from serial ventricular taps in premature neonates with severe IVH and subsequent PHH. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein were quantified using ELISA. Ventriculomegaly on cranial imaging was assessed using the frontal occipital horn ratio (FOHR) and was categorized as severe (FOHR > 0.6) or moderate (FOHR ≤ 0.6)., Results: Ventricular tap CSF hemoglobin (mean) and ferritin (initial and mean) were higher in neonates with severe versus moderate initial ventriculomegaly. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein decreased in a nonlinear fashion over the weeks following severe IVH. Significantly higher levels of CSF ferritin and total iron were observed in the early weeks following IVH in neonates with severe initial ventriculomegaly than in those with initial moderate ventriculomegaly., Conclusions: Among preterm neonates with PHH following severe IVH, elevated CSF hemoglobin, ferritin, and iron were associated with more severe early ventricular enlargement (FOHR > 0.6 vs ≤ 0.6 at first ventricular tap).
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- 2022
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46. Pathogenic variant in NFIA associated with subdural hematomas mimicking nonaccidental trauma.
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Wongkittichote P, Kondis JS, Peglar LM, Strahle JM, Miller-Thomas M, and Abell KB
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- Diagnosis, Differential, Humans, Infant, Hematoma, Subdural diagnosis, Hematoma, Subdural genetics, NFI Transcription Factors
- Abstract
Subdural hematoma (SDH) in infants raises the concern for nonaccidental trauma (NAT), especially when presenting with associated injuries. However, isolated SDH could be caused by multiple etiologies. NFIA (MIM# 600727) encodes nuclear factor I A protein (NFI-A), a transcription factor which plays important roles in gliogenesis. Loss-of-function variants in NFIA are associated with autosomal dominant brain malformations with or without urinary tract defects (MIM# 613735). Intracranial hemorrhage of various types besides SDH has been reported in patients with this condition. Here, we report a patient with a heterozygous novel NFIA pathogenic variant affecting splicing who initially presented with SDH concerning for NAT. We also review previous NFIA-related disorder cases with intracranial hemorrhage. This report emphasizes the importance of genetic evaluation in infants presenting with isolated SDH., (© 2022 Wiley Periodicals LLC.)
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- 2022
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47. Leptomeningeal disease and tumor dissemination in a murine diffuse intrinsic pontine glioma model: implications for the study of the tumor-cerebrospinal fluid-ependymal microenvironment.
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Pan S, Ye D, Yue Y, Yang L, Pacia CP, DeFreitas D, Esakky P, Dahiya S, Limbrick DD, Rubin JB, Chen H, and Strahle JM
- Abstract
Background: Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor-CSF-ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG., Methods: A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic alterations (H3.3K27M, PDGF-B, and p53) was used for this study. All mice underwent MR imaging and a subset underwent histopathologic analysis with H&E and immunostaining., Results: Tumor dissemination within the CSF pathways (ventricles, leptomeninges) from the subependyma was present in 76% (25/33) of mice, with invasion of the choroid plexus, disruption of the ciliated ependyma and regional subependymal fluid accumulation. Ventricular enlargement consistent with hydrocephalus was present in 94% (31/33). Ventricle volume correlated with region-specific transependymal CSF flow (periventricular T2 signal), localized anterior to the lateral ventricles., Conclusions: This is the first study to report CSF pathway tumor dissemination associated with subependymal tumor in an animal model of DIPG and is representative of CSF dissemination seen clinically. Understanding the CSF-tumor-ependymal microenvironment has significant implications for treatment of DIPG through targeting mechanisms of tumor spread within the CSF pathways., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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- 2022
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48. Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.
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Akbari SHA, Yahanda AT, Ackerman LL, Adelson PD, Ahmed R, Albert GW, Aldana PR, Alden TD, Anderson RCE, Bauer DF, Bethel-Anderson T, Bierbrauer K, Brockmeyer DL, Chern JJ, Couture DE, Daniels DJ, Dlouhy BJ, Durham SR, Ellenbogen RG, Eskandari R, Fuchs HE, Grant GA, Graupman PC, Greene S, Greenfield JP, Gross NL, Guillaume DJ, Hankinson TC, Heuer GG, Iantosca M, Iskandar BJ, Jackson EM, Jallo GI, Johnston JM, Kaufman BA, Keating RF, Khan NR, Krieger MD, Leonard JR, Maher CO, Mangano FT, McComb JG, McEvoy SD, Meehan T, Menezes AH, Muhlbauer MS, O'Neill BR, Olavarria G, Ragheb J, Selden NR, Shah MN, Shannon CN, Shimony JS, Smyth MD, Stone SSD, Strahle JM, Tamber MS, Torner JC, Tuite GF, Tyler-Kabara EC, Wait SD, Wellons JC, Whitehead WE, Park TS, and Limbrick DD
- Abstract
Objective: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM)., Methods: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups., Results: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD., Conclusions: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.
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- 2022
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49. Superficial abdominal reflex in syringomyelia: Associations with Chiari I malformation.
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Nadel JL, Ziats C, Mossner JM, Starr JB, Smith BW, Kelly MP, Muraszko KM, Farley FA, Maher CO, Garton HJL, and Strahle JM
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- Child, Humans, Magnetic Resonance Imaging adverse effects, Reflex, Abdominal physiology, Reflex, Abnormal, Retrospective Studies, Arnold-Chiari Malformation complications, Arnold-Chiari Malformation diagnostic imaging, Scoliosis etiology, Syringomyelia complications, Syringomyelia diagnostic imaging
- Abstract
An abnormal or absent superficial abdominal reflex (SAR) may be associated with an underlying spinal cord syrinx. The sensitivity of an abnormal or absent SAR and the relationship to Chiari malformation type I (CM-I) or syrinx morphology has not been studied. We aimed to describe the relationship between SAR abnormalities and syrinx size, location, and etiology. Children who underwent brain or c-spine MRI over 11 years were reviewed in this retrospective cohort study. Patients with idiopathic and CM-I-associated syringes (axial diameter ≥ 3 mm) were included. Clinical examination findings (including SAR) and imaging characteristics were analyzed. Of 271 patients with spinal cord syrinx, 200 had either CM-I-associated or idiopathic syrinx, and 128 of these patients had SAR-evaluation documentation. Forty-eight percent (62/128) had an abnormal or absent reflex. Abnormal/absent SAR was more common in patients with CM-I-associated syrinx (61%) compared with idiopathic syrinx (22%) (P < 0.0001). Abnormal/absent SAR was associated with wider syringes (P < 0.001), longer syringes (P < 0.05), and a more cranial location of the syrinx (P < 0.0001). Controlling for CM-I, scoliosis, age, sex, cranial extent of syrinx, and syrinx dimensions, CM-I was independently associated with abnormal or absent SAR (OR 4.2, 95% CI 1.4-14, P < 0.01). Finally, the sensitivity of SAR for identifying a patient with syrinx was 48.1%. An abnormal/absent SAR was present in most patients with CM-I-associated syrinx but in a minority of patients with idiopathic syrinx. This has implications for pathophysiology of CM-I-associated syrinx and in guiding clinical care of patients presenting with syrinx., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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50. Representation of female neurosurgeons as abstract authors at neurological surgery conferences.
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Johnson GW, Almgren-Bell A, Skidmore A, Raval D, Blow G, Gu H, Mackey K, Groves M, Lee H, and Strahle JM
- Abstract
Objective: Female neurosurgeon representation has increased, but women still represent only 8.4% of neurosurgeons in the US. Women are significantly underrepresented as authors in neurosurgical and spine journals, a key indicator of professional success in academic medicine. In this study, the authors aimed to assess the gender diversity of first and last authors of accepted abstracts at neurosurgical conferences in 2015 and 2019., Methods: Annual meeting abstracts for 2015 and 2019 of the American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS), and pediatrics, spine, stereotactic and functional surgery, and cerebrovascular AANS/CNS subspecialty sections were obtained and analyzed for gender. Partial data were obtained for tumor and pain sections. Composite gender data were obtained from the societies. Percentage differences were calculated using comparison of proportions testing., Results: Overall, female neurosurgeons accounted for only 8.3% of first and 5.8% of last authors, and 7.2% of authors overall. The pediatrics section had the highest proportion of female neurosurgeons as first (13.7%) and last (12.4%) abstract authors, while the spine section had the lowest proportions of female neurosurgeon first (4.6%) and last (2.0%) authors. Qualitatively, a higher proportion of women were first authors, while a higher proportion of men were last authors. Overall, there was no significant change in female neurosurgeon authorship between 2015 and 2019. With regard to society demographics, female neurosurgeons accounted for only 6.3% of AANS membership. The pediatrics section had the highest proportion of female neurosurgeons at 18.1% and the stereotactic and functional surgery section had the lowest of the subspecialty sections (7.6%). While female neurosurgeons represented 12.6% of spine section membership, they represented only 4.7% of first authors (-7.9% difference; p < 0.0001) and 2.4% of last authors (-10.2% difference; p < 0.0001). For the 2019 cerebrovascular section, female neurosurgeons were underrepresented as presenting authors (5.8%) compared with their membership representation (14.8%, -9.0% difference; p = 0.0018)., Conclusions: Despite an increase in the number of female neurosurgeons, there has not been a corresponding increase in the proportion of female neurosurgeons as abstract authors at annual neurosurgery conferences, and female neurosurgeons remain underrepresented as authors compared with their male colleagues.
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- 2022
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