Publications by authors named "D D Limbrick"

192 Publications

Outcomes for various dural graft materials after posterior fossa decompression with duraplasty for Chiari malformation type I: a systematic review and meta-analysis.

J Neurosurg 2021 Apr 9:1-14. Epub 2021 Apr 9.

Departments of1Neurological Surgery and.

Objective: Posterior fossa decompression with duraplasty (PFDD) is often used for Chiari malformation type I (CM-I), but outcomes associated with different dural graft materials are not well characterized. In this meta-analysis, the authors examined complication rates and outcomes after PFDD for CM-I for autografts and four types of nonautologous grafts.

Methods: A literature search of numerous electronic databases (Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, and ClinicalTrials.gov) was performed to identify articles detailing complications for dural graft materials after PFDD. Whenever available, data were also extracted regarding the need for revision surgery, symptom changes after PFDD, and syrinx size changes after PFDD. All searches were compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Institute of Medicine, Standards for Systematic Reviews, Cochrane Handbook for Systematic Reviews of Interventions, and Peer Review of Electronic Search Strategies guidelines. There were no exclusion criteria based on patient age or presence or absence of syringomyelia.

Results: The current evidence surrounding outcomes for various dural graft materials was found to be of low or very low quality. Twenty-seven studies were included, encompassing 1461 patients. Five types of dural graft materials were included: autograft (n = 404, 27.6%), synthetic (n = 272, 18.6%), bovine pericardium (n = 181, 12.4%), collagen-based (n = 397, 27.2%), and allograft (n = 207, 14.2%). Autograft was associated with a significantly lower rate of pseudomeningocele compared to collagen-based grafts, allografts, and nonautologous grafts in aggregate. Autograft was also associated with the lowest rates of aseptic meningitis, infectious meningitis, and need for revision PFDD, though these associations did not reach statistical significance. No other graft comparisons yielded significant results. Autograft and nonautologous graft materials yielded similar rates of revision surgery and produced similar improvements in postoperative symptoms and syrinx size.

Conclusions: Autograft was the dural graft material that most frequently had the lowest rate of complications and was associated with significantly lower rates of pseudomeningocele compared to collagen-based graft, allograft, and nonautologous graft materials. Autografts and nonautologous grafts yielded similar outcomes for revision surgery, symptoms, and syrinx size. Large prospective studies comparing different graft materials are needed to accurately and precisely characterize outcomes for individual graft types.
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http://dx.doi.org/10.3171/2020.9.JNS202641DOI Listing
April 2021

Development of best practices in the utilization and implementation of pediatric cervical spine traction: a modified Delphi study.

J Neurosurg Pediatr 2021 Apr 2:1-12. Epub 2021 Apr 2.

1Department of Neurological Surgery, Columbia University Medical Center, New York, New York.

Objective: Cervical traction in pediatric patients is an uncommon but invaluable technique in the management of cervical trauma and deformity. Despite its utility, little empirical evidence exists to guide its implementation, with most practitioners employing custom or modified adult protocols. Expert-based best practices may improve the care of children undergoing cervical traction. In this study, the authors aimed to build consensus and establish best practices for the use of pediatric cervical traction in order to enhance its utilization, safety, and efficacy.

Methods: A modified Delphi method was employed to try to identify areas of consensus regarding the utilization and implementation of pediatric cervical spine traction. A literature review of pediatric cervical traction was distributed electronically along with a survey of current practices to a group of 20 board-certified pediatric neurosurgeons and orthopedic surgeons with expertise in the pediatric cervical spine. Sixty statements were then formulated and distributed to the group. The results of the second survey were discussed during an in-person meeting leading to further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).

Results: After the initial round, consensus was achieved with 40 statements regarding the following topics: goals, indications, and contraindications of traction (12), pretraction imaging (6), practical application and initiation of various traction techniques (8), protocols in trauma and deformity patients (8), and management of traction-related complications (6). Following the second round, an additional 9 statements reached consensus related to goals/indications/contraindications of traction (4), related to initiation of traction (4), and related to complication management (1). All participants were willing to incorporate the consensus statements into their practice.

Conclusions: In an attempt to improve and standardize the use of cervical traction in pediatric patients, the authors have identified 49 best-practice recommendations, which were generated by reaching consensus among a multidisciplinary group of pediatric spine experts using a modified Delphi technique. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.
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http://dx.doi.org/10.3171/2020.10.PEDS20778DOI Listing
April 2021

Hydrocephalus treatment in patients with craniosynostosis: an analysis from the Hydrocephalus Clinical Research Network prospective registry.

Neurosurg Focus 2021 Apr;50(4):E11

1Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Objective: Hydrocephalus may be seen in patients with multisuture craniosynostosis and, less commonly, single-suture craniosynostosis. The optimal treatment for hydrocephalus in this population is unknown. In this study, the authors aimed to evaluate the success rate of ventriculoperitoneal shunt (VPS) treatment and endoscopic third ventriculostomy (ETV) both with and without choroid plexus cauterization (CPC) in patients with craniosynostosis.

Methods: Utilizing the Hydrocephalus Clinical Research Network (HCRN) Core Data Project (Registry), the authors identified all patients who underwent treatment for hydrocephalus associated with craniosynostosis. Descriptive statistics, demographics, and surgical outcomes were evaluated.

Results: In total, 42 patients underwent treatment for hydrocephalus associated with craniosynostosis. The median gestational age at birth was 39.0 weeks (IQR 38.0, 40.0); 55% were female and 60% were White. The median age at first craniosynostosis surgery was 0.6 years (IQR 0.3, 1.7), and at the first permanent hydrocephalus surgery it was 1.2 years (IQR 0.5, 2.5). Thirty-three patients (79%) had multiple different sutures fused, and 9 had a single suture: 3 unicoronal (7%), 3 sagittal (7%), 2 lambdoidal (5%), and 1 unknown (2%). Syndromes were identified in 38 patients (90%), with Crouzon syndrome being the most common (n = 16, 42%). Ten patients (28%) received permanent hydrocephalus surgery before the first craniosynostosis surgery. Twenty-eight patients (67%) underwent VPS treatment, with the remaining 14 (33%) undergoing ETV with or without CPC (ETV ± CPC). Within 12 months after initial hydrocephalus intervention, 14 patients (34%) required revision (8 VPS and 6 ETV ± CPC). At the most recent follow-up, 21 patients (50%) required a revision. The revision rate decreased as age increased. The overall infection rate was 5% (VPS 7%, 0% ETV ± CPC).

Conclusions: This is the largest prospective study reported on children with craniosynostosis and hydrocephalus. Hydrocephalus in children with craniosynostosis most commonly occurs in syndromic patients and multisuture fusion. It is treated at varying ages; however, most patients undergo surgery for craniosynostosis prior to hydrocephalus treatment. While VPS treatment is performed more frequently, VPS and ETV are both reasonable options, with decreasing revision rates with increasing age, for the treatment of hydrocephalus associated with craniosynostosis.
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http://dx.doi.org/10.3171/2021.1.FOCUS20979DOI Listing
April 2021

Immediate Postoperative Electroencephalography Monitoring in Pediatric Moyamoya Disease and Syndrome.

Pediatr Neurol 2021 Feb 15;118:40-45. Epub 2021 Feb 15.

Department of Neurosurgery, Washington University in St. Louis, St. Louis, Missouri.

Background: Moyamoya disease and syndrome are progressive steno-occlusive cerebrovascular diseases that manifest clinically with ischemic episodes. There is evidence for the use of electroencephalography (EEG) in preoperative and long-term postoperative evaluation of these patients, as well as in the intraoperative period to monitor for changes correlated with perioperative ischemic events. However, the utility of EEG in the immediate postprocedure time period has not previously been described.

Methods: We review six patients who underwent pial synangiosis from 2017 to 2019. EEGs from the preoperative, intraoperative, and immediate postoperative period were evaluated, as well as clinical examination changes and subsequent interventions.

Results: Six patients with postoperative EEG monitoring following pial synangiosis were included. EEG data was collected preoperatively, intraoperatively, and continuously postoperatively. Preoperatively, five of six patients had normal background activity on EEG, whereas one of six had hemispheric asymmetry. Three patients had new or worsening hemispheric intracerebral asymmetry on EEG during the immediate postsurgical period. Two of these had no clinical manifestations of ischemia, and one had transient left facial weakness. All three underwent blood pressure augmentation with improvement in the asymmetry on EEG and clinical improvement in the symptomatic patient.

Conclusions: Although widely accepted as a useful tool during the preoperative and intraoperative periods of evaluation and management of moyamoya disease and syndrome, we propose that the use of continuous EEG in the immediate postoperative period may have potential as a useful adjunct by both detecting early clinical and subclinical intracranial ischemia.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.02.004DOI Listing
February 2021

Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity.

PLoS One 2021 10;16(3):e0247749. Epub 2021 Mar 10.

Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States of America.

Objective: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH.

Study Design: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15-30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson's partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores.

Results: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966).

Conclusion: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247749PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946285PMC
March 2021

MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus.

Neuroimage Clin 2021 Feb 2;30:102579. Epub 2021 Feb 2.

Montefiore Medical Center, Department of Neurosurgery, Bronx, NY, USA.

Introduction: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

Methods: MRE was collected at two imaging sites in 39 hydrocephalus patients and 33 healthy controls, along with demographic, shunt-related, and clinical outcome measures including headache and quality of life indices. Brain stiffness was quantified for whole brain, global white matter (WM), and lobar WM stiffness. Group differences in brain stiffness between patients and controls were compared using two-sample t-tests and multivariable linear regression to adjust for age, sex, and ventricular volume. Among patients, multivariable linear or logistic regression was used to assess which factors (age, sex, ventricular volume, age at first shunt, number of shunt revisions) were associated with brain stiffness and whether brain stiffness predicts clinical outcomes (quality of life, headache and depression).

Results: Brain stiffness was significantly reduced in patients compared to controls, both unadjusted (p ≤ 0.002) and adjusted (p ≤ 0.03) for covariates. Among hydrocephalic patients, lower stiffness was associated with older age in temporal and parietal WM and whole brain (WB) (beta (SE): -7.6 (2.5), p = 0.004; -9.5 (2.2), p = 0.0002; -3.7 (1.8), p = 0.046), being female in global and frontal WM and WB (beta (SE): -75.6 (25.5), p = 0.01; -66.0 (32.4), p = 0.05; -73.2 (25.3), p = 0.01), larger ventricular volume in global, and occipital WM (beta (SE): -11.5 (3.4), p = 0.002; -18.9 (5.4), p = 0.0014). Lower brain stiffness also predicted worse quality of life and a higher likelihood of depression, controlling for all other factors.

Conclusions: Brain stiffness is reduced in hydrocephalus patients compared to healthy controls, and is associated with clinically-relevant functional outcome measures. MRE may emerge as a clinically-relevant biomarker to assess the neuropathological effects of hydrocephalus and shunting, and may be useful in evaluating the effects of therapeutic alternatives, or as a supplement, of shunting.
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http://dx.doi.org/10.1016/j.nicl.2021.102579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905205PMC
February 2021

Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: a Park-Reeves Syringomyelia Research Consortium study.

J Neurosurg Pediatr 2021 Feb 12:1-10. Epub 2021 Feb 12.

1Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO.

Objective: Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM.

Methods: The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft.

Results: A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain.

Conclusions: In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.
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http://dx.doi.org/10.3171/2020.8.PEDS2087DOI Listing
February 2021

Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction.

Fluids Barriers CNS 2021 Jan 29;18(1). Epub 2021 Jan 29.

Division of Pediatric Neurosurgery, and Department of Pediatrics, Department of Neurosurgery, Washington University in St. Louis, 425 S. Euclid, St. Louis, MO, 63110, USA.

Background: Approximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus.

Methods: Using multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-α, GM-CSF, IFN-γ. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg/mL for each analyte.

Results: Patient CSF was obtained at the time of shunt revision operation; all pediatric (< 18), totaling n = 38. IL-10, IL-6, IL-8 and MMP-7 demonstrated significantly increased concentrations in patient CSF for the non-obstructed subgroup. Etiological examination revealed IL-6 was increased in both obstructed and non-obstructed cases for PHH and congenital hydrocephalic patients, while IL-8 was higher only in PHH patients. In terms of number of past revisions, IL-10, IL-6, IL-8, MMP-7 and MMP-9 progressively increased from zero to two past revisions and then remained low for subsequent revisions. This presentation was notably absent in the obstruction subgroup. Shunts implanted for three months or less showed significantly increased concentrations of IL-6, IL-8, and MMP-7 in the obstruction subgroup. Lastly, only patients aged six months or less presented with significantly increased concentration of IL-8 and MMP-7.

Conclusion: Non-obstructive cases are reported here to accompany significantly higher CSF cytokine and MMP protein levels compared to obstructive cases for IL-10, IL-6, IL-8, MMP-7 and MMP-9. A closer examination of the definition of obstruction and the role neuroinflammation plays in creating shunt obstruction in hydrocephalic patients is suggested.
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http://dx.doi.org/10.1186/s12987-021-00237-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845119PMC
January 2021

Characterization of cerebrospinal fluid (CSF) microbiota from patients with CSF shunt infection and reinfection using high throughput sequencing of 16S ribosomal RNAgenes.

PLoS One 2021 6;16(1):e0244643. Epub 2021 Jan 6.

Department of Pediatrics, Keck School of Medicine at the University of Southern California, Los Angeles, California, United States of America.

Background: Nearly 20% of patients with cerebrospinal fluid (CSF) shunt infection develop reinfection. It is unclear whether reinfections are caused by an organism previously present or are independent infection events.

Objective: We used bacterial culture and high throughput sequencing (HTS) of 16S ribosomal RNA (rRNA) genes to identify bacteria present in serial CSF samples obtained from children who failed CSF shunt infection treatment. We hypothesized that organisms that persist in CSF despite treatment would be detected upon reinfection.

Design/methods: Serial CSF samples were obtained from 6 patients, 5 with 2 infections and 1 with 3 infections; the study was limited to those for which CSF samples were available from the end of infection and beginning of reinfection. Amplicons of the 16S rRNA gene V4 region were sequenced. Taxonomic assignments of V4 sequences were compared with bacterial species identified in culture.

Results: Seven infection dyads averaging 13.5 samples per infection were analyzed. A median of 8 taxa [interquartile range (IQR) 5-10] were observed in the first samples from reinfection using HTS. Conventional culture correlated with high abundance of an organism by HTS in all but 1 infection. In 6 of 7 infection dyads, organisms identified by culture at reinfection were detected by HTS of culture-negative samples at the end of the previous infection. The median Chao-Jaccard abundance-based similarity index for matched infection pairs at end of infection and beginning of reinfection was 0.57 (IQR 0.07-0.87) compared to that for unmatched pairs of 0.40 (IQR 0.10-0.60) [p = 0.46].

Conclusion(s): HTS results were generally consistent with culture-based methods in CSF shunt infection and reinfection, and may detect organisms missed by culture at the end of infection treatment but detected by culture at reinfection. However, the CSF microbiota did not correlate more closely within patients at the end of infection and beginning of reinfection than between any two unrelated infections. We cannot reject the hypothesis that sequential infections were independent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244643PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787469PMC
January 2021

Rare and de novo coding variants in chromodomain genes in Chiari I malformation.

Am J Hum Genet 2021 01 21;108(1):100-114. Epub 2020 Dec 21.

Department of Neurosurgery, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University, St. Louis, MO 63110, USA; Department of Genetics, Washington University, St. Louis, MO 63110, USA. Electronic address:

Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses. A significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes was observed among individuals with CM1 (combined p = 2.4 × 10), including 3 de novo loss-of-function variants in CHD8 (LOF enrichment p = 1.9 × 10) and a significant burden of rare transmitted variants in CHD3 (p = 1.8 × 10). Overall, individuals with CM1 were found to have significantly increased head circumference (p = 2.6 × 10), with many harboring CHD rare variants having macrocephaly. Finally, haploinsufficiency for chd8 in zebrafish led to macrocephaly and posterior hindbrain displacement reminiscent of CM1. These results implicate chromodomain genes and excessive brain growth in CM1 pathogenesis.
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http://dx.doi.org/10.1016/j.ajhg.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820723PMC
January 2021

Temporal trends in surgical procedures for pediatric hydrocephalus: an analysis of the Hydrocephalus Clinical Research Network Core Data Project.

J Neurosurg Pediatr 2020 Dec 18:1-8. Epub 2020 Dec 18.

9Department of Clinical Neurosciences, Alberta Children's Hospital, University of Calgary, Alberta, Canada.

Objective: Analysis of temporal trends in patient populations and procedure types may provide important information regarding the evolution of hydrocephalus treatment. The purpose of this study was to use the Hydrocephalus Clinical Research Network's Core Data Project to identify meaningful trends in patient characteristics and the surgical management of pediatric hydrocephalus over a 9-year period.

Methods: The Core Data Project prospectively collected patient and procedural data on the study cohort from 9 centers between 2008 and 2016. Logistic and Poisson regression were used to test for significant temporal trends in patient characteristics and new and revision hydrocephalus procedures.

Results: The authors analyzed 10,149 procedures in 5541 patients. New procedures for hydrocephalus (shunt or endoscopic third ventriculostomy [ETV]) decreased by 1.5%/year (95% CI -3.1%, +0.1%). During the study period, new shunt insertions decreased by 6.5%/year (95% CI -8.3%, -4.6%), whereas new ETV procedures increased by 12.5%/year (95% CI 9.3%, 15.7%). Revision procedures for hydrocephalus (shunt or ETV) decreased by 4.2%/year (95% CI -5.2%, -3.1%), driven largely by a decrease of 5.7%/year in shunt revisions (95% CI -6.8%, -4.6%). Concomitant with the observed increase in new ETV procedures was an increase in ETV revisions (13.4%/year, 95% CI 9.6%, 17.2%). Because revisions decreased at a faster rate than new procedures, the Revision Quotient (ratio of revisions to new procedures) for the Network decreased significantly over the study period (p = 0.0363). No temporal change was observed in the age or etiology characteristics of the cohort, although the proportion of patients with one or more complex chronic conditions significantly increased over time (p = 0.0007).

Conclusions: Over a relatively short period, important changes in hydrocephalus care have been observed. A significant temporal decrease in revision procedures amid the backdrop of a more modest change in new procedures appears to be the most notable finding and may be indicative of an improvement in the quality of surgical care for pediatric hydrocephalus. Further studies will be directed at elucidation of the possible drivers of the observed trends.
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http://dx.doi.org/10.3171/2020.7.PEDS20142DOI Listing
December 2020

Predictors of fast and ultrafast shunt failure in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

J Neurosurg Pediatr 2020 Dec 18:1-10. Epub 2020 Dec 18.

2Division of Pediatric Neurosurgery, Department of Neurosurgery, Primary Children's Medical Center, University of Utah, Salt Lake City, Utah.

Objective: The primary objective of this study was to use the prospective Hydrocephalus Clinical Research Network (HCRN) registry to determine clinical predictors of fast time to shunt failure (≤ 30 days from last revision) and ultrafast time to failure (≤ 7 days from last revision).

Methods: Revisions (including those due to infection) to permanent shunt placements that occurred between April 2008 and November 2017 for patients whose entire shunt experience was recorded in the registry were analyzed. All registry data provided at the time of initial shunt placement and subsequent revision were reviewed. Key variables analyzed included etiology of hydrocephalus, age at time of initial shunt placement, presence of slit ventricles on imaging at revision, whether the ventricles were enlarged at the time of revision, and presence of prior fast failure events. Univariable and multivariable analyses were performed to find key predictors of fast and ultrafast failure events.

Results: A cohort of 1030 patients with initial shunt insertions experienced a total of 1995 revisions. Of the 1978 revision events with complete records, 1216 (61.5%) shunts remained functional for more than 1 year, and 762 (38.5%) failed within 1 year of the procedure date. Of those that failed within 1 year, 423 (55.5%) failed slowly (31-365 days) and 339 (44.5%) failed fast (≤ 30 days). Of the fast failures, 131 (38.6%) were ultrafast (≤ 7 days). In the multivariable analysis specified a priori, etiology of hydrocephalus (p = 0.005) and previous failure history (p = 0.011) were independently associated with fast failure. Age at time of procedure (p = 0.042) and etiology of hydrocephalus (p = 0.004) were independently associated with ultrafast failure. These relationships in both a priori models were supported by the data-driven multivariable models as well.

Conclusions: Neither the presence of slit ventricle syndrome nor ventricular enlargement at the time of shunt failure appears to be a significant predictor of repeated, rapid shunt revisions. Age at the time of procedure, etiology of hydrocephalus, and the history of previous failure events seem to be important predictors of fast and ultrafast shunt failure. Further work is required to understand the mechanisms of these risk factors as well as mitigation strategies.
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http://dx.doi.org/10.3171/2020.7.PEDS20111DOI Listing
December 2020

Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium.

Neurosurgery 2021 01;88(2):332-341

Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology.

Objective: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD.

Methods: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD.

Results: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P < .001) were increased within the OCF group, whereas only basilar invagination (1/4, P < .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P = .008) and OCF/VD (115.0 ± 11.6°, P = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups.

Conclusion: Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.
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http://dx.doi.org/10.1093/neuros/nyaa460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803430PMC
January 2021

Tract-Specific Relationships Between Cerebrospinal Fluid Biomarkers and Periventricular White Matter in Posthemorrhagic Hydrocephalus of Prematurity.

Neurosurgery 2021 02;88(3):698-706

Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.

Background: Posthemorrhagic hydrocephalus (PHH) is associated with neurological morbidity and complex neurosurgical care. Improved tools are needed to optimize treatments and to investigate the developmental sequelae of PHH.

Objective: To examine the relationship between diffusion magnetic resonance imaging (dMRI) and cerebrospinal fluid (CSF) biomarkers of PHH.

Methods: A total of 14 preterm (PT) infants with PHH and 46 controls were included. PT CSF was collected at temporizing surgery in PHH infants (PHH PT CSF) or lumbar puncture in controls. Term-equivalent age (TEA) CSF was acquired via implanted device or at permanent CSF diversion surgery in PHH (PHH-TEA-CSF) or lumbar puncture in controls. TEA dMRI scans were used to measure fractional anisotropy (FA) and mean diffusivity (MD) in the genu of corpus callosum (gCC), posterior limb of internal capsule (PLIC), and optic radiations (OPRA). Associations between dMRI measures and CSF amyloid precursor protein (APP), neural cell adhesion-1 (NCAM-1), and L1 cell adhesion molecule (L1CAM) were assessed using Pearson correlations.

Results: APP, NCAM-1, and L1CAM were elevated over controls in PHH-PT-CSF and PHH-TEA-CSF. dMRI FA and MD differed between control and PHH infants across all tracts. PHH-PT-CSF APP levels correlated with gCC and OPRA FA and PLIC MD, while L1CAM correlated with gCC and OPRA FA. In PHH-TEA-CSF, only L1CAM correlated with OPRA MD.

Conclusion: Tract-specific associations were observed between dMRI and CSF biomarkers at the initiation of PHH treatment. dMRI and CSF biomarker analyses provide innovative complementary methods for examining PHH-related white matter injury and associated developmental sequelae.
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http://dx.doi.org/10.1093/neuros/nyaa466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884147PMC
February 2021

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Nat Med 2020 11 19;26(11):1754-1765. Epub 2020 Oct 19.

Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
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http://dx.doi.org/10.1038/s41591-020-1090-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871900PMC
November 2020

Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images.

Sci Rep 2020 10 9;10(1):16885. Epub 2020 Oct 9.

Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, 80045, USA.

Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.
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http://dx.doi.org/10.1038/s41598-020-73278-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547020PMC
October 2020

infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

Sci Transl Med 2020 09;12(563)

Center for Neural Engineering, Pennsylvania State University, University Park, PA 16802, USA.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium , together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference strain. These findings show that an unbiased pan-microbial approach enabled characterization of in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.
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http://dx.doi.org/10.1126/scitranslmed.aba0565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774825PMC
September 2020

Semi-automated segmentation of the lateral periventricular regions using diffusion magnetic resonance imaging.

MethodsX 2020 20;7:101023. Epub 2020 Aug 20.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.

The lateral ventricular perimeter (LVP) of the brain is a critical region because in addition to housing neural stem cells required for brain development, it facilitates cerebrospinal fluid (CSF) bulk flow and functions as a blood-CSF barrier to protect periventricular white matter (PVWM) and other adjacent regions from injurious toxins. LVP injury is common, particularly among preterm infants who sustain intraventricular hemorrhage or post hemorrhagic hydrocephalus and has been associated with poor neurological outcomes. Assessment of the LVP with diffusion MRI has been challenging, primarily due to issues with partial volume artifacts since the LVP region is in close proximity to CSF and other structures of varying signal intensities that may be inadvertently included in LVP segmentation. This research method presents:•A novel MATLAB-based method to segment a homogenous LVP layer using high spatial resolution parameters (voxel size 1.2 × 1.2 × 1.2 mm) to only capture the innermost layer of the LVP.•The segmented LVP is averaged from three contiguous axial slices to increase signal to noise ratio and reduce the effect of any residual volume averaging effect and eliminates manual and inter/intrarater-related errors.
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http://dx.doi.org/10.1016/j.mex.2020.101023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492999PMC
August 2020

Use of fast-sequence spine MRI in pediatric patients.

J Neurosurg Pediatr 2020 Sep 18:1-6. Epub 2020 Sep 18.

1Department of Neurological Surgery and.

Objective: The immediate and long-term risk of anesthesia in the pediatric population is controversial. Traditional spine MRI protocols require the patient to remain still during the examination, and in young children this frequently results in the need for sedation administration. The authors' goal was to develop an abbreviated spine MRI protocol to reduce sedation administration in young patients undergoing spine MRI.

Methods: After IRB approval, the medical records of all pediatric patients who underwent a fast spine MRI protocol between 2017 and 2019 were reviewed. The protocol consisted of T2-weighted half-Fourier acquisition single-shot turbo spin echo, T1-weighted turbo spin echo, and T2-weighted STIR sequences acquired in the sagittal plane. The total acquisition time was 2 minutes with no single sequence acquisition longer than 60 seconds. Interpretability of the scans was assessed in accordance with the radiology report in conjunction with the neurosurgeon's clinical notes.

Results: A total of 47 fast spine MRI sessions were performed in 45 patients. The median age at the time of the MRI was 2.4 years (25th-75th quartile, 1.1-4.3 years; range 0.16-18.58 years). The most common indication for imaging was to rule out or follow a known syrinx (n = 30), followed by the need to rule out or follow known spinal dysraphism (n = 22). There were no uninterpretable or unusable scans. Eight of 47 scans were noted to have moderate motion artifact limitations with respect to the quality of the scan. Seven patients underwent a subsequent MRI with a sedated standard spine protocol within 1 year from the fast scan, which confirmed the findings on the fast MRI protocol with no new findings identified.

Conclusions: The authors report the first pediatric series of a fast spine MRI protocol for use in young patients. The protocol does not require sedation and is able to identify and monitor syrinx, spinal dysraphism, and potentially other intraspinal anomalies.
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http://dx.doi.org/10.3171/2020.5.PEDS20137DOI Listing
September 2020

Using Histopathology to Assess the Reliability of Intraoperative Magnetic Resonance Imaging in Guiding Additional Brain Tumor Resection: A Multicenter Study.

Neurosurgery 2020 12;88(1):E49-E59

Washington University School of Medicine, St. Louis, Missouri.

Background: Intraoperative magnetic resonance imaging (iMRI) is a powerful tool for guiding brain tumor resections, provided that it accurately discerns residual tumor.

Objective: To use histopathology to assess how reliably iMRI may discern additional tumor for a variety of tumor types, independent of the indications for iMRI.

Methods: A multicenter database was used to calculate the odds of additional resection during the same surgical session for grade I to IV gliomas and pituitary adenomas. The reliability of iMRI for identifying residual tumor was assessed using histopathology of tissue resected after iMRI.

Results: Gliomas (904/1517 cases, 59.6%) were more likely than pituitary adenomas (176/515, 34.2%) to receive additional resection after iMRI (P < .001), but these tumors were equally likely to have additional tissue sent for histopathology (398/904, 44.4% vs 66/176, 37.5%; P = .11). Tissue samples were available for resections after iMRI for 464 cases, with 415 (89.4%) positive for tumor. Additional resections after iMRI for gliomas (361/398, 90.7%) were more likely to yield additional tumor compared to pituitary adenomas (54/66, 81.8%) (P = .03). There were no significant differences in resection after iMRI yielding histopathologically positive tumor between grade I (58/65 cases, 89.2%; referent), grade II (82/92, 89.1%) (P = .98), grade III (72/81, 88.9%) (P = .95), or grade IV gliomas (149/160, 93.1%) (P = .33). Additional resection for previously resected tumors (122/135 cases, 90.4%) was equally likely to yield histopathologically confirmed tumor compared to newly-diagnosed tumors (293/329, 89.0%) (P = .83).

Conclusion: Histopathological analysis of tissue resected after use of iMRI for grade I to IV gliomas and pituitary adenomas demonstrates that iMRI is highly reliable for identifying residual tumor.
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http://dx.doi.org/10.1093/neuros/nyaa338DOI Listing
December 2020

Management of Post-hemorrhagic Ventricular Dilatation in the Infant Born Preterm.

J Pediatr 2020 Jul 30. Epub 2020 Jul 30.

Department of Neonatology, University Medical Center Utrecht, the Netherlands; University Medical Center Utrecht, Utrecht Brain Center, the Netherlands.

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http://dx.doi.org/10.1016/j.jpeds.2020.07.079DOI Listing
July 2020

Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study.

Neurosurgery 2020 12;88(1):63-73

Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri.

Background: Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas.

Objective: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas.

Methods: Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS.

Results: A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P < .001) and PFS (P = .01) than astrocytomas. Multivariate analyses demonstrated improved OS for gross total resection (GTR) vs subtotal resection (STR; P = .006, hazard ratio [HR]: .23) and near total resection (NTR; P = .02, HR: .64). GTR vs STR (P = .02, HR: .54), GTR vs NTR (P = .04, HR: .49), and iMRI use (P = .02, HR: .54) were associated with longer PFS. Frontal (P = .048, HR: 2.11) and occipital/parietal (P = .003, HR: 3.59) locations were associated with shorter PFS (vs temporal). Kaplan-Meier analyses showed longer OS with increasing extent of surgical resection (EOR) (P = .03) and 1p/19q gene deletions (P = .02). PFS improved with increasing EOR (P = .01), GTR vs NTR (P = .02), and resections above STR (P = .04). Factors influencing adjuvant treatment (35.3% of patients) included age (P = .002, odds ratio [OR]: 1.04) and EOR (P = .003, OR: .39) but not glioma subtype or location. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these instances.

Conclusion: EOR is a major determinant of OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS.
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http://dx.doi.org/10.1093/neuros/nyaa320DOI Listing
December 2020

Preterm intraventricular hemorrhage in vitro: modeling the cytopathology of the ventricular zone.

Fluids Barriers CNS 2020 Jul 20;17(1):46. Epub 2020 Jul 20.

Department of Neurological Surgery, Washington University School of Medicine and the St. Louis Children's Hospital, Campus Box 8057, 660 South Euclid Ave., St. Louis, MO, 63110, USA.

Background: Severe intraventricular hemorrhage (IVH) is one of the most devastating neurological complications in preterm infants, with the majority suffering long-term neurological morbidity and up to 50% developing post-hemorrhagic hydrocephalus (PHH). Despite the importance of this disease, its cytopathological mechanisms are not well known. An in vitro model of IVH is required to investigate the effects of blood and its components on the developing ventricular zone (VZ) and its stem cell niche. To address this need, we developed a protocol from our accepted in vitro model to mimic the cytopathological conditions of IVH in the preterm infant.

Methods: Maturing neuroepithelial cells from the VZ were harvested from the entire lateral ventricles of wild type C57BL/6 mice at 1-4 days of age and expanded in proliferation media for 3-5 days. At confluence, cells were re-plated onto 24-well plates in differentiation media to generate ependymal cells (EC). At approximately 3-5 days, which corresponded to the onset of EC differentiation based on the appearance of multiciliated cells, phosphate-buffered saline for controls or syngeneic whole blood for IVH was added to the EC surface. The cells were examined for the expression of EC markers of differentiation and maturation to qualitatively and quantitatively assess the effect of blood exposure on VZ transition from neuroepithelial cells to EC.

Discussion: This protocol will allow investigators to test cytopathological mechanisms contributing to the pathology of IVH with high temporal resolution and query the impact of injury to the maturation of the VZ. This technique recapitulates features of normal maturation of the VZ in vitro, offering the capacity to investigate the developmental features of VZ biogenesis.
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http://dx.doi.org/10.1186/s12987-020-00210-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372876PMC
July 2020

Characterization of a multicenter pediatric-hydrocephalus shunt biobank.

Fluids Barriers CNS 2020 Jul 18;17(1):45. Epub 2020 Jul 18.

Wayne State University Dept. of Chemical Engineering and Materials Science, 6135 Woodward Avenue, Rm 1413, Detroit, MI, 48202, USA.

Background: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

Methods: To date, four hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus before adulthood. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. Data such as hydrocephalus etiology and details of shunt revision history. All data are entered under a coded identifier.

Results: 293 shunt samples were collected from 228 pediatric patients starting from May 2015 to September 2019. We saw a significant difference in the number of revisions per patient between centers (Kruskal-Wallis H test, p value < 0.001). The leading etiology at all centers was post-hemorrhagic hydrocephalus, a fisher's exact test showed there to be statistically significant differences in etiology between center (p = 0.01). Regression showed age (p < 0.01), race (p = 0.038) and hospital-center (p < 0.001) to explain significant variance in the number of revisions. Our model accounted for 31.9% of the variance in revisions. Generalized linear modeling showed hydrocephalus etiology (p < 0.001), age (p < 0.001), weight and physician (p < 0.001) to impact the number of ventricular obstructions.

Conclusion: The retrospective analysis identified that differences exist between currently enrolled centers, although further work is needed before clinically actionable recommendations can be made. Moreover, the variables collected from this chart review explain a meaningful amount of variance in the number of revision surgeries. Future work will expand on the contribution of different site-specific and patient-specific factors to identify potential cause and effect relationships.
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http://dx.doi.org/10.1186/s12987-020-00211-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368709PMC
July 2020

Surgical resource utilization after initial treatment of infant hydrocephalus: comparing ETV, early experience of ETV with choroid plexus cauterization, and shunt insertion in the Hydrocephalus Clinical Research Network.

J Neurosurg Pediatr 2020 Jun 19:1-9. Epub 2020 Jun 19.

4Department of Neurosurgery, University of Utah, Salt Lake City, Utah.

Objective: Few studies have addressed surgical resource utilization-surgical revisions and associated hospital admission days-following shunt insertion or endoscopic third ventriculostomy (ETV) with or without choroid plexus cauterization (CPC) for CSF diversion in hydrocephalus. Study members of the Hydrocephalus Clinical Research Network (HCRN) investigated differences in surgical resource utilization between CSF diversion strategies in hydrocephalus in infants.

Methods: Patients up to corrected age 24 months undergoing initial definitive treatment of hydrocephalus were reviewed from the prospectively maintained HCRN Core Data Project (Hydrocephalus Registry). Postoperative courses (at 1, 3, and 5 years) were studied for hydrocephalus-related surgeries (primary outcome) and hospital admission days related to surgical revision (secondary outcome). Data were summarized using descriptive statistics and compared using negative binomial regression, controlling for age, hydrocephalus etiology, and HCRN center. The study population was organized into 3 groups (ETV alone, ETV with CPC, and CSF shunt insertion) during the 1st postoperative year and 2 groups (ETV alone and CSF shunt insertion) during subsequent years due to limited long-term follow-up data.

Results: Among 1090 patients, the majority underwent CSF shunt insertion (CSF shunt, 83.5%; ETV with CPC, 10.0%; and ETV alone, 6.5%). Patients undergoing ETV with CPC had a higher mean number of revision surgeries (1.2 ± 1.6) than those undergoing ETV alone (0.6 ± 0.8) or CSF shunt insertion (0.7 ± 1.3) over the 1st year after surgery (p = 0.005). At long-term follow-up, patients undergoing ETV alone experienced a nonsignificant lower mean number of revision surgeries (0.7 ± 0.9 at 3 years and 0.8 ± 1.3 at 5 years) than those undergoing CSF shunt insertion (1.1 ± 1.9 at 3 years and 1.4 ± 2.6 at 5 years) and exhibited a lower mean number of hospital admission days related to revision surgery (3.8 ± 10.3 vs 9.9 ± 27.0, p = 0.042).

Conclusions: Among initial treatment strategies for hydrocephalus, ETV with CPC yielded a higher surgical revision rate within 1 year after surgery. Patients undergoing ETV alone exhibited a nonsignificant lower mean number of surgical revisions than CSF shunt insertion at 3 and 5 years postoperatively. Additionally, the ETV-alone cohort demonstrated significantly fewer hospital admission days related to surgical management of hydrocephalus within 3 years after surgery. These findings suggest a time-dependent benefit of ETV over CSF shunt insertion regarding surgical resource utilization.
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http://dx.doi.org/10.3171/2020.4.PEDS19632DOI Listing
June 2020

Comparison of anticoagulation and antiplatelet therapy for treatment of blunt cerebrovascular injury in children <10 years of age: a multicenter retrospective cohort study.

Childs Nerv Syst 2021 Jan 29;37(1):47-54. Epub 2020 May 29.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT, 84132, USA.

Purpose: Blunt cerebrovascular injury (BCVI) is uncommon in the pediatric population. Among the management options is medical management consisting of antithrombotic therapy with either antiplatelets or anticoagulation. There is no consensus on whether administration of antiplatelets or anticoagulation is more appropriate for BCVI in children < 10 years of age. Our goal was to compare radiographic and clinical outcomes based on medical treatment modality for BCVI in children < 10 years.

Methods: Clinical and radiographic data were collected retrospectively for children screened for BCVI with computed tomography angiography at 5 academic pediatric trauma centers.

Results: Among 651 patients evaluated with computed tomography angiography to screen for BCVI, 17 patients aged less than 10 years were diagnosed with BCVI (7 grade I, 5 grade II, 1 grade III, 4 grade IV) and received anticoagulation or antiplatelet therapy for 18 total injuries: 11 intracranial carotid artery, 4 extracranial carotid artery, and 3 extracranial vertebral artery injuries. Eleven patients were treated with antiplatelets (10 aspirin, 1 clopidogrel) and 6 with anticoagulation (4 unfractionated heparin, 2 low-molecular-weight heparin, 1 transitioned from the former to the latter). There were no complications secondary to treatment. One patient who received anticoagulation died as a result of the traumatic injuries. In aggregate, children treated with antiplatelet therapy demonstrated healing on 52% of follow-up imaging studies versus 25% in the anticoagulation cohort.

Conclusion: There were no observed differences in the rate of hemorrhagic complications between anticoagulation and antiplatelet therapy for BCVI in children < 10 years, with a nonsignificantly better rate of healing on follow-up imaging in children who underwent antiplatelet therapy; however, the study cohort was small despite including patients from 5 hospitals.
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http://dx.doi.org/10.1007/s00381-020-04672-wDOI Listing
January 2021

Association between supratentorial pediatric high-grade gliomas involved with the subventricular zone and decreased survival: a multi-institutional retrospective study.

J Neurosurg Pediatr 2020 May 22:1-7. Epub 2020 May 22.

1Department of Neurological Surgery, Vanderbilt University Medical Center.

Objective: The subventricular zone (SVZ), housed in the lateral walls of the lateral ventricles, is the largest neurogenic niche in the brain. In adults, high-grade gliomas in contact or involved with the SVZ are associated with decreased survival. Whether this association holds true in the pediatric population remains unexplored. To address this gap in knowledge, the authors conducted this retrospective study in a pediatric population with high-grade gliomas treated at three comprehensive centers in the United States.

Methods: The authors retrospectively identified 63 patients, age ≤ 21 years, with supratentorial WHO grade III-IV gliomas treated at three academic centers. Basic demographic and clinical data regarding presenting signs and symptoms and common treatment variables were obtained. Preoperative MRI studies were evaluated to assess SVZ contact by tumor and to quantify tumor volume.

Results: Sixty-three patients, including 34 males (54%), had a median age of 12.3 years (IQR 6.50-16.2) and a median tumor volume of 39.4 ml (IQR 19.4-65.8). Tumors contacting the SVZ (SVZ+) were noted in 34 patients (54%) and overall were larger than those not in contact with the SVZ (SVZ-; 51.1 vs 27.3, p = 0.002). The SVZ+ tumors were also associated with decreased survival. However, age, tumor volume, tumor grade, and treatment with chemotherapy and/or radiation were not associated with survival in the 63 patients. In the univariable analysis, near-total resection, gross-total resection, and seizure presentation were associated with increased survival (HR = 0.23, 95% CI 0.06-0.88, p = 0.03; HR = 0.26, 95% CI 0.09-0.74, p = 0.01; and HR = 0.46, 95% CI 0.22-0.97, p = 0.04, respectively). In a multivariable stepwise Cox regression analysis, only SVZ+ tumors remained significantly associated with decreased survival (HR = 1.94, 95% CI 1.03-3.64, p = 0.04).

Conclusions: High-grade glioma contact with the SVZ neural stem cell niche was associated with a significant decrease in survival in the pediatric population, as it is in the adult population. This result suggests that tumor contact with the SVZ is a general negative prognosticator in high-grade glioma independent of age group and invites biological investigations to understand the SVZ's role in glioma pathobiology.
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http://dx.doi.org/10.3171/2020.3.PEDS19593DOI Listing
May 2020