Publications by authors named "Robert P Naftel"

74 Publications

Genome-Wide Association Study Identifies Genetic Risk Factors for Spastic Cerebral Palsy.

Neurosurgery 2021 Aug;89(3):435-442

Surgical Outcomes Center for Kids, Monroe Carell Jr Children's Hospital of Vanderbilt University, Nashville, Tennessee, USA.

Background: Although many clinical risk factors of spastic cerebral palsy (CP) have been identified, the genetic basis of spastic CP is largely unknown. Here, using whole-genome genetic information linked to a deidentified electronic health record (BioVU) with replication in the UK Biobank and FinnGen, we perform the first genome-wide association study (GWAS) for spastic CP.

Objective: To define the genetic basis of spastic CP.

Methods: Whole-genome data were obtained using the multi-ethnic genotyping array (MEGA) genotyping array capturing single-nucleotide polymorphisms (SNPs), minor allele frequency (MAF) > 0.01, and imputation quality score (r2) > 0.3, imputed based on the 1000 genomes phase 3 reference panel. Threshold for genome-wide significance was defined after Bonferroni correction for the total number of SNPs tested (P < 5.0 × 10-8). Replication analysis (defined as P < .05) was performed in the UK Biobank and FinnGen.

Results: We identify 1 SNP (rs78686911) reaching genome-wide significance with spastic CP. Expression quantitative trait loci (eQTL) analysis suggests that rs78686911 decreases expression of GRIK4, a gene that encodes a high-affinity kainate glutamatergic receptor of largely unknown function. Replication analysis in the UK Biobank and FinnGen reveals additional SNPs in the GRIK4 loci associated with CP.

Conclusion: To our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.
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http://dx.doi.org/10.1093/neuros/nyab184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364821PMC
August 2021

Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

Ann Neurol 2021 Aug 25;90(2):217-226. Epub 2021 Jun 25.

Department of Neurosurgery, Washington University St. Louis, St. Louis, MO, USA.

Objective: Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group.

Methods: This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes.

Results: Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p = 0.015) and decreased CSF hemopexin (p = 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p = 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p = 0.04) and motor (p = 0.03) scores and improved cognitive (p = 0.04), language (p = 0.035), and motor (p = 0.008) scores, respectively.

Interpretation: Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.
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http://dx.doi.org/10.1002/ana.26133DOI Listing
August 2021

Choice and Trade-offs: Parent Decision Making for Neurotechnologies for Pediatric Drug-Resistant Epilepsy.

J Child Neurol 2021 Oct 2;36(11):943-949. Epub 2021 Jun 2.

8166University of British Columbia, Division of Neurology, Department of Medicine, Vancouver, British Columbia, Canada.

This qualitative study investigated factors that guide caregiver decision making and ethical trade-offs for advanced neurotechnologies used to treat children with drug-resistant epilepsy. Caregivers with affected children were recruited to semi-structured focus groups or interviews at one of 4 major epilepsy centers in Eastern and Western Canada and the USA (n = 22). Discussions were transcribed and qualitative analytic methods applied to examine values and priorities (eg, risks, benefits, adherence, invasiveness, reversibility) of caregivers pertaining to novel technologies to treat drug-resistant epilepsy. Discussions revealed 3 major thematic branches for decision making: (1) features of the intervention-risks and benefits, with an emphasis on an aversion to perceived invasiveness; (2) decision drivers-trust in the clinical team, treatment costs; and (3) quality of available information about neurotechnological options. Overall, caregivers' definition of treatment success is more expansive than seizure freedom. The full involvement of their values and priorities must be considered in the decision-making process.
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http://dx.doi.org/10.1177/08830738211015010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458226PMC
October 2021

Pediatric Intrathecal Baclofen Pumps: A Descriptive Analysis of Hospital Course and Associated Costs.

Pediatr Neurosurg 2021 7;56(4):334-344. Epub 2021 May 7.

Surgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.

Introduction: The purpose of this study was to identify predictors of increased cost and postoperative length-of-stay (LOS) following intrathecal baclofen pump (ITBP) placement.

Methods: Patients were derived from the 2009/2012 kids' inpatient database. Inclusion criteria were selected for patients with ICD-9 codes 343.X (infantile cerebral palsy), 86.06 (infusion pump insertion), 03.90 (spinal catheter insertion), and elective hospitalizations. Nonparametric univariate analysis and subsequent gamma log-link general linear modeling were used to identify significant predictors of cost/LOS (p < 0.05).

Results: 529 unweighted patients (787 with survey weights applied) met criteria. Median LOS was 3.00 days, and median cost was USD 23,284. Following multivariate modeling, predictors of increased LOS (in days) included increased hospital ITBP volume (p = 0.027), small hospital size (+0.55, p = 0.004), device complications (+0.95, p < 0.001), procedural complications (+1.40, p < 0.001), additional procedures (+0.86, p < 0.001), electrolyte abnormalities (+3.74, p < 0.001), and neurological comorbidities (+1.60, p < 0.001). Factors associated with decreased LOS were paralysis (-0.53, p < 0.001), Northeastern hospital region (-0.55, p = 0.018), and investor-owned hospital status (-0.75, p = 0.001). Similarly, predictors of increased cost included race of Hispanic (+USD 1,156, p = 0.033) or "other" (+USD 2,158, p = 0.001), Northeast hospital region (+USD 4,120, p < 0.001), small (+USD 4,139, p < 0.001) or medium (+USD 3,368, p < 0.001) hospital sizes, additional procedures (+USD 1,649, p < 0.001), neurological comorbidities (+USD 3,222, p = 0.003), and increased LOS (p < 0.001). Factors associated with decreased cost included Western hospital region (-USD 1,594, p = 0.001), government hospitals (-USD 1,391, p = 0.019), and investor-owned hospitals (-USD 2,057, p = 0.021).

Conclusion: This study found multiple variables associated with increased cost/LOS following ITBP placement. Broadly, this analysis demonstrates national trends associated with increased cost following ITBP placement.
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http://dx.doi.org/10.1159/000515988DOI Listing
May 2021

Treatment strategies for hydrocephalus related to Dandy-Walker syndrome: evaluating procedure selection and success within the Hydrocephalus Clinical Research Network.

J Neurosurg Pediatr 2021 Apr 30:1-9. Epub 2021 Apr 30.

16Neurosurgery, University of Utah, Salt Lake City, Utah.

Objective: Treating Dandy-Walker syndrome-related hydrocephalus (DWSH) involves either a CSF shunt-based or endoscopic third ventriculostomy (ETV)-based procedure. However, comparative investigations are lacking. This study aimed to compare shunt-based and ETV-based treatment strategies utilizing archival data from the Hydrocephalus Clinical Research Network (HCRN) registry.

Methods: A retrospective review of prospectively collected and maintained data on children with DWSH, available from the HCRN registry (14 sites, 2008-2018), was performed. The primary outcome was revision-free survival of the initial surgical intervention. The primary exposure was either shunt-based (i.e., cystoperitoneal shunt [CPS], ventriculoperitoneal shunt [VPS], and/or dual-compartment) or ETV-based (i.e., ETV alone or with choroid plexus cauterization [CPC]) initial surgical treatment. Primary analysis included multivariable Cox proportional hazards models.

Results: Of 8400 HCRN patients, 151 (1.8%) had DWSH. Among these, the 102 patients who underwent shunt placement (79 VPSs, 16 CPSs, 3 other, and 4 multiple proximal catheter) were younger (6.6 vs 18.8 months, p < 0.001) and more frequently had 1 or more comorbidities (37.3% vs 14.3%, p = 0.005) than the 49 ETV-treated children (28 ETV-CPC). Fifty percent of the shunt-based and 51% of the ETV-based treatments failed. Notably, 100% (4/4) of the dual-compartment shunts failed. Adjusting for age, baseline ventricular size, and comorbidities, ETV-based treatment was not significantly associated with earlier failure compared with shunt-based treatment (HR for failure 1.32, 95% CI 0.77-2.26; p = 0.321). Complication rates were low: 4.9% and 6.1% (p = 0.715) for shunt- and ETV-based procedures, respectively. There was no difference in survival between ETV-CPC- and ETV-based treatment when adjusting for age (HR for failure 0.86, 95% CI 0.29-2.55, p = 0.783).

Conclusions: In this North American, multicenter, prospective database review, shunt-based and ETV-based primary treatment strategies of DWSH appear similarly durable. Pediatric neurosurgeons can reasonably consider ETV-based initial treatment given the similar durability and the low complication rate. However, given the observational nature of this study, the treating surgeon might need to consider subgroups that were too small for a separate analysis. Very young children with comorbidities were more commonly treated with shunts, and older children with fewer comorbidities were offered ETV-based treatment. Future studies may determine preoperative characteristics associated with ETV treatment success in this population.
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http://dx.doi.org/10.3171/2020.11.PEDS20806DOI Listing
April 2021

Mechatronic Design of a Two-Arm Concentric Tube Robot System for Rigid Neuroendoscopy.

IEEE ASME Trans Mechatron 2020 Jun 27;25(3):1432-1443. Epub 2020 Feb 27.

Department of Mechanical Engineering at Vanderbilt University, Nashville, TN 37235, USA.

Open surgical approaches are still often employed in neurosurgery, despite the availability of neuroendoscopic approaches that reduce invasiveness. The challenge of maneuvering instruments at the tip of the endoscope makes neuroendoscopy demanding for the physician. The only way to aim tools passed through endoscope ports is to tilt the entire endoscope; but, tilting compresses brain tissue through which the endoscope passes and can damage it. Concentric tube robots can provide necessary dexterity without endoscope tilting, while passing through existing ports in the endoscope and carrying surgical tools in their inner lumen. In this paper we describe the mechatronic design of a new concentric tube robot that can deploy two concentric tube manipulators through a standard neuroendoscope. The robot uses a compact differential drive and features embedded motor control electronics and redundant position sensors for safety. In addition to the mechatronic design of this system, this paper contributes experimental validation in the context of colloid cyst removal, comparing our new robotic system to standard manual endoscopy in a brain phantom. The robotic approach essentially eliminated endoscope tilt during the procedure (17.09° for the manual approach vs. 1.16° for the robotic system). The robotic system also enables a single surgeon to perform the procedure - typically in a manual approach one surgeon aims the endoscope and another operates the tools delivered through its ports.
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http://dx.doi.org/10.1109/tmech.2020.2976897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971161PMC
June 2020

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
September 2021

The survival of reimplanted shunts following externalization: a single-institution cohort study.

J Neurosurg Pediatr 2021 Feb 12:1-9. Epub 2021 Feb 12.

1Department of Neurological Surgery, Vanderbilt University Medical Center; and.

Objective: The failure-free survival of ventriculoperitoneal shunts (VPSs) following externalization for distal catheter infection or malfunction has not been adequately explored. Conversion to a ventriculoatrial shunt (VAS) may allow earlier reinternalization in lieu of waiting for the peritoneum to be suitable for reimplantation. This option is tempered by historical concerns regarding high rates of VAS failure, and the risks of rare complications are rampant.

Methods: In this retrospective cohort study, all patients undergoing externalization of a VPS at a single institution between 2005 and 2020 were grouped according to the new distal catheter terminus location at the time of reinternalization (VPS vs VAS). The primary outcomes were failure-free shunt survival and duration of shunt externalization. Secondary outcomes included early (< 6 months) shunt failure.

Results: Among 36 patients, 43 shunt externalization procedures were performed. Shunts were reinternalized as VPSs in 25 cases and VASs in 18 cases. The median failure-free survival was 1002 (interquartile range [IQR] 161-3449) days for VPSs and 1163 (IQR 360-2927) days for VASs. There was no significant difference in shunt survival according to the new distal catheter terminus (log-rank, p = 0.73). Conversion to a VAS was not associated with shorter duration of shunt externalization (Wilcoxon rank-sum, p = 0.64); the median duration was 7 (IQR 5-11) days for VPSs and 8 (IQR 6-15) days for VASs. No rare complications occurred in the VAS group.

Conclusions: Shunt failure-free survival rates following externalization are similar to published survival rates for nonexternalized shunts. There was no significant difference in survival between reinternalized VPSs and VASs. Although the VAS was not associated with a shortened duration of externalization, this finding is confounded by strong institutional preference for the VPS over the VAS. Early conversion to the VAS may be a viable treatment option in light of reassuring modern VAS survival data.
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http://dx.doi.org/10.3171/2020.8.PEDS20533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357850PMC
February 2021

Machine learning predicts risk of cerebrospinal fluid shunt failure in children: a study from the hydrocephalus clinical research network.

Childs Nerv Syst 2021 05 30;37(5):1485-1494. Epub 2021 Jan 30.

Surgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital of Vanderbilt University, Nashville, TN, USA.

Purpose: While conventional statistical approaches have been used to identify risk factors for cerebrospinal fluid (CSF) shunt failure, these methods may not fully capture the complex contribution of clinical, radiologic, surgical, and shunt-specific variables influencing this outcome. Using prospectively collected data from the Hydrocephalus Clinical Research Network (HCRN) patient registry, we applied machine learning (ML) approaches to create a predictive model of CSF shunt failure.

Methods: Pediatric patients (age < 19 years) undergoing first-time CSF shunt placement at six HCRN centers were included. CSF shunt failure was defined as a composite outcome including requirement for shunt revision, endoscopic third ventriculostomy, or shunt infection within 5 years of initial surgery. Performance of conventional statistical and 4 ML models were compared.

Results: Our cohort consisted of 1036 children undergoing CSF shunt placement, of whom 344 (33.2%) experienced shunt failure. Thirty-eight clinical, radiologic, surgical, and shunt-design variables were included in the ML analyses. Of all ML algorithms tested, the artificial neural network (ANN) had the strongest performance with an area under the receiver operator curve (AUC) of 0.71. The ANN had a specificity of 90% and a sensitivity of 68%, meaning that the ANN can effectively rule-in patients most likely to experience CSF shunt failure (i.e., high specificity) and moderately effective as a tool to rule-out patients at high risk of CSF shunt failure (i.e., moderately sensitive). The ANN was independently validated in 155 patients (prospectively collected, retrospectively analyzed).

Conclusion: These data suggest that the ANN, or future iterations thereof, can provide an evidence-based tool to assist in prognostication and patient-counseling immediately after CSF shunt placement.
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http://dx.doi.org/10.1007/s00381-021-05061-7DOI Listing
May 2021

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

Novel Neurotechnological Interventions for Pediatric Drug-Resistant Epilepsy: Physician Perspectives.

J Child Neurol 2021 03 28;36(3):222-229. Epub 2020 Oct 28.

8166University of British Columbia, Division of Neurology, Department of Medicine, Vancouver, British Columbia, Canada.

This qualitative study investigated factors that guide physicians' choices for minimally invasive and neuromodulatory interventions as alternatives to conventional surgery or medical management for pediatric drug-resistant epilepsy. North American physicians were recruited to one of 4 focus groups at national conferences. Discussions were analyzed using qualitative content analysis. A pragmatic neuroethics framework was applied to interpret results. Discussions revealed 2 major thematic branches: (1) clinical decision making and (2) ethical considerations. Under clinical decision making, physicians emphasized scientific evidence and patient candidacy when assessing neurotechnologies for patients. Ongoing seizures without intervention was important for safety and neurodevelopment. Under ethical considerations, resource allocation, among other financial considerations for technology adoption, were considerable sources of pressure on decision making. Access to neurotechnology was a salient theme differentiating Canadian and American contexts. When assessing novel neurotechnological interventions for pediatric drug-resistant epilepsy, physicians balance clinical and ethical factors to guide decision making and best practice.
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http://dx.doi.org/10.1177/0883073820966935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855396PMC
March 2021

An algorithmic approach to preoperative studies and patient selection for hemispheric disconnection surgery: a literature review.

Epileptic Disord 2020 Oct;22(5):592-609

Northeast Regional Epilepsy Group, Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, NJ, USA.

Hemispheric disconnection surgery (HDS) is one of the most effective surgical options for appropriate candidates with medically-refractory epilepsy (MRE) in whom most or all seizures arise from diffuse areas within a single hemisphere. While there are several well-accepted indications for HDS, there are additional patients who may benefit from HDS. However, there are no standardized recommendations for how preoperative studies should be used to identify appropriate candidates for HDS. We aimed to propose an algorithmic approach for presurgical evaluation in order to guide appropriate implementation of HDS for either cure or palliation of severe MRE in infants, children, and adults. We performed a qualitative review of the literature using PubMed, the Cochrane Library, and Google Scholar to select primary articles addressing imaging modalities used for the presurgical evaluation of patients with MRE being considered for HDS. In total, we identified 126 articles that met our inclusion criteria. We propose a framework to guide candidate selection for HDS that incorporates various elements of the clinical presentation, electroencephalographic analysis, and neuroimaging. While this approach still requires prospective validation, the authors feel it is grounded in a synthesis of the best available evidence in the literature and informed by expert opinion. HDS is a powerful tool in the armamentarium of experienced multi-disciplinary epilepsy centers to treat patients with severe MRE arising from diffuse areas constrained to a single hemisphere. The under-utilization of epilepsy surgery may be, in part, remedied by establishing evidence-based pathways for presurgical analyses to determine surgical candidacy.
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http://dx.doi.org/10.1684/epd.2020.1205DOI Listing
October 2020

Conus-level combined dorsal and ventral lumbar rhizotomy for treatment of mixed hypertonia: technical note and complications.

J Neurosurg Pediatr 2020 Oct 9:1-6. Epub 2020 Oct 9.

2Surgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital.

Combined dorsal and ventral rhizotomy is an effective treatment for patients with concurrent spasticity and dystonia, with the preponderance of complaints relating to their lower extremities. This operative approach provides definitive relief of hypertonia and should be considered after less-invasive techniques have been exhausted. Previously, the surgery has been described through an L1-S1 laminoplasty. In this series, 7 patients underwent a conus-level laminectomy for performing a lumbar dorsal and ventral rhizotomy. Technical challenges included identifying the appropriate-level ventral roots and performing the procedure in children with significant scoliosis. Techniques are described to overcome these obstacles. The technique was found to be safe, with no infections, CSF leaks, or neurogenic bladders.
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http://dx.doi.org/10.3171/2020.6.PEDS20295DOI Listing
October 2020

The interaction between parental concern and socioeconomic status in pediatric hydrocephalus management.

J Neurosurg Pediatr 2020 Oct 9:1-7. Epub 2020 Oct 9.

1Department of Neurological Surgery, Division of Pediatric Neurosurgery, and.

Objective: Parent or guardian involvement is implicit in the care of pediatric patients with hydrocephalus. Some parents and guardians are more engaged than others. The relationship between socioeconomic status (SES), the level of parental concern about their child's hydrocephalus management and future, and overall health status has not been clearly delineated. In this study, the authors sought to clarify this connection using hydrocephalus patient-reported health outcomes.

Methods: This cross-sectional study included children with surgically managed hydrocephalus whose parent or guardian completed the validated Hydrocephalus Outcome Questionnaire (HOQ) and Hydrocephalus Concern Questionnaire for parents (HCQ-P) on a return visit to the pediatric neurosurgery clinic at Vanderbilt University Medical Center between 2016 and 2018. Patients were excluded if the questionnaires were not completed in full. The calculated Overall Health Score (OHS) was used to represent the child's global physical, emotional, cognitive, and social health. The HCQ-P was used to assess parental concern about their child. Type of insurance was a proxy for SES.

Results: The HOQ and HCQ-P were administered and completed in full by 170 patient families. In the cohort, 91% of patients (n = 155) had shunt-treated hydrocephalus, and the remaining patients had undergone endoscopic third ventriculostomy. The mean (± SD) patient age was 12 ± 4 years. Half of the patients were male (n = 90, 53%), and most were Caucasian (n = 134, 79%). One in four patients lived in single-parent homes or with a designated guardian (n = 45, 26%). Public insurance and self-pay accounted for 38% of patients (n = 64), while the remaining 62% had private or military insurance. In general, parents with higher concern about their child's medical condition indicated that their son or daughter had a higher OHS (χ2 = 17.07, p < 0.001). Patients in families with a lower SES did not have different OHSs from those with a higher SES (χ2 = 3.53, p = 0.06). However, parents with a lower SES were more worried about management of their child's hydrocephalus and their child's future success (χ2 = 11.49, p < 0.001). In general, parents were not preoccupied with one particular aspect of their child's hydrocephalus management.

Conclusions: More engaged parents, regardless of their family's SES, reported a better OHS for their child. Parents with public or self-paid insurance were more likely to report higher concern about their child's hydrocephalus and future, but this was not associated with a difference in their child's current health status.
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http://dx.doi.org/10.3171/2020.6.PEDS20191DOI Listing
October 2020

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

Epilepsia 2020 11 18;61(11):2534-2544. Epub 2020 Sep 18.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Objective: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity.

Methods: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity.

Results: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes.

Significance: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.
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http://dx.doi.org/10.1111/epi.16686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899016PMC
November 2020

Patient and parental assessment of factors influencing the choice of treatment in pediatric hydrocephalus.

J Neurosurg Pediatr 2020 Aug 7:1-5. Epub 2020 Aug 7.

2Vanderbilt University Medical Center, Nashville, Tennessee.

Objective: Choosing between competing options (shunt or endoscopic third ventriculostomy) for the management of hydrocephalus requires patients and caregivers to make a subjective judgment about the relative importance of risks and benefits associated with each treatment. In the context of this particular decision, little is known about what treatment-related factors are important and how they are prioritized in order to arrive at a treatment preference.

Methods: The Hydrocephalus Association electronically distributed a survey to surgically treated hydrocephalus patients or their families. Respondents rated the importance of various surgical attributes in their decision-making about treatment choice, and also indicated their preference in hypothetical scenarios involving a trade-off between potential risks and benefits of treatment. Rank-order correlations were used to determine whether certain predictor variables affected the rating of factors or hypothetical treatment choice.

Results: Eighty percent of 414 respondents rated procedural risks, minimizing repeat surgery, and improving long-term brain function as being very or extremely important factors when deciding on a treatment; 69% rated the need to implant a permanent device similarly. Parent-respondents rated procedural risks higher than patient-respondents. A majority of respondents (n = 209, 54%) chose a procedure with higher surgical risk if it meant that implantation of a permanent device was not required, and respondents were more likely to choose this option if they discussed both treatment options with their surgeon prior to their initial intervention (Spearman rho 0.198, p = 0.001).Although only 144 of 384 total respondents (38%) chose a less established operation if it meant less repeat surgery, patient-respondents were more likely to choose this option compared to parent-respondents (Spearman rho 0.145, p = 0.005). Likewise, patient-respondents were more likely than parent-respondents to choose an operation that involved less repeat surgery and led to worse long-term brain function (Spearman rho 0.160, p = 0.002), an option that was chosen by only 23 (6%) of respondents overall.

Conclusions: This study is the first exploration of patient/parental factors that influence treatment preference in pediatric hydrocephalus. Procedural risks, minimizing repeat operations, and the desire to maximize long-term cognitive function appeared to be the most important attributes that influenced treatment decisions that the survey respondents had made in the past. Patients and/or their caregivers appear to see some inherent benefit in being shunt free. It appears that fear of multiple revision operations may drive treatment choice in some circumstances.
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http://dx.doi.org/10.3171/2020.5.PEDS2095DOI Listing
August 2020

In Reply to the Letter to the Editor Regarding "Global Diversity and Academic Success of Foreign-Trained Academic Neurosurgeons in the United States".

World Neurosurg 2020 07;139:706

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Division of Pediatric Neurosurgery, Monroe Carell Jr. Children's Hospital, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.04.174DOI Listing
July 2020

Tracking the Volume of Neurosurgical Care During the Coronavirus Disease 2019 Pandemic.

World Neurosurg 2020 10 27;142:e183-e194. Epub 2020 Jun 27.

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

Objective: In the present study, we quantified the effect of the coronavirus disease 2019 (COVID-19) on the volume of adult and pediatric neurosurgical procedures, inpatient consultations, and clinic visits at an academic medical center.

Methods: Neurosurgical procedures, inpatient consultations, and outpatient appointments at Vanderbilt University Medical Center were identified from March 23, 2020 through May 8, 2020 (during COVID-19) and March 25, 2019 through May 10, 2019 (before COVID-19). The neurosurgical volume was compared between the 2 periods.

Results: A 40% reduction in weekly procedural volume was demonstrated during COVID-19 (median before, 75; interquartile range [IQR], 72-80; median during, 45; IQR, 43-47; P < 0.001). A 42% reduction occurred in weekly adult procedures (median before, 62; IQR, 54-70; median during, 36; IQR, 34-39; P < 0.001), and a 31% reduction occurred in weekly pediatric procedures (median before, 13; IQR, 12-14; median during, 9; IQR, 8-10; P = 0.004). Among adult procedures, the most significant decreases were seen for spine (P < 0.001) and endovascular (P < 0.001) procedures and cranioplasty (P < 0.001). A significant change was not found in the adult open vascular (P = 0.291), functional (P = 0.263), cranial tumor (P = 0.143), or hydrocephalus (P = 0.173) procedural volume. Weekly inpatient consultations to neurosurgery decreased by 24% (median before, 99; IQR, 94-114; median during, 75; IQR, 68-84; P = 0.008) for adults. Weekly in-person adult and pediatric outpatient clinic visits witnessed a 91% decrease (median before, 329; IQR, 326-374; median during, 29; IQR, 26-39; P < 0.001). In contrast, weekly telehealth encounters increased from a median of 0 (IQR, 0-0) before to a median of 151 (IQR, 126-156) during COVID-19 (P < 0.001).

Conclusions: Significant reductions occurred in neurosurgical operations, clinic visits, and inpatient consultations during COVID-19. Telehealth was increasingly used for assessments. The long-term effects of the reduced neurosurgical volume and increased telehealth usage on patient outcomes should be explored.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319935PMC
October 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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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 01 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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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

Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets.

Acta Neuropathol Commun 2020 05 13;8(1):68. Epub 2020 May 13.

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

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.
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http://dx.doi.org/10.1186/s40478-020-00939-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222517PMC
May 2020

Timing of syrinx reduction and stabilization after posterior fossa decompression for pediatric Chiari malformation type I.

J Neurosurg Pediatr 2020 Apr 24:1-7. Epub 2020 Apr 24.

1Department of Neurosurgery, Vanderbilt University Medical Center.

Objective: The aim of this study was to determine the timeline of syrinx regression and to identify factors mitigating syrinx resolution in pediatric patients with Chiari malformation type I (CM-I) undergoing posterior fossa decompression (PFD).

Methods: The authors conducted a retrospective review of records from pediatric patients (< 18 years old) undergoing PFD for the treatment of CM-I/syringomyelia (SM) between 1998 and 2015. Patient demographic, clinical, radiological, and surgical variables were collected and analyzed. Radiological information was reviewed at 4 time points: 1) pre-PFD, 2) within 6 months post-PFD, 3) within 12 months post-PFD, and 4) at maximum available follow-up. Syrinx regression was defined as ≥ 50% decrease in the maximal anteroposterior syrinx diameter (MSD). The time to syrinx regression was determined using Kaplan-Meier analysis. Multivariate analysis was conducted using a Cox proportional hazards model to determine the association between preoperative, clinical, and surgery-related factors and syrinx regression.

Results: The authors identified 85 patients with CM-I/SM who underwent PFD. Within 3 months post-PFD, the mean MSD regressed from 8.1 ± 3.4 mm (preoperatively) to 5.6 ± 2.9 mm within 3 months post-PFD. Seventy patients (82.4%) achieved ≥ 50% regression in MSD. The median time to ≥ 50% regression in MSD was 8 months (95% CI 4.2-11.8 months). Using a risk-adjusted multivariable Cox proportional hazards model, the patients who underwent tonsil coagulation (n = 20) had a higher likelihood of achieving ≥ 50% syrinx regression in a shorter time (HR 2.86, 95% CI 1.2-6.9; p = 0.02). Thirty-six (75%) of 45 patients had improvement in headache at 2.9 months (IQR 1.5-4.4 months).

Conclusions: The maximum reduction in syrinx size can be expected within 3 months after PFD for patients with CM-I and a syrinx; however, the syringes continue to regress over time. Tonsil coagulation was associated with early syrinx regression in this cohort. However, the role of surgical maneuvers such as tonsil coagulation and arachnoid veil identification and sectioning in the overall role of CM-I surgery remains unclear.
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http://dx.doi.org/10.3171/2020.2.PEDS19366DOI Listing
April 2020

Graft dural closure is associated with a reduction in CSF leak and hydrocephalus in pediatric patients undergoing posterior fossa brain tumor resection.

J Neurosurg Pediatr 2019 Nov 29:1-7. Epub 2019 Nov 29.

2Surgical Outcomes Center for Kids, and.

Objective: The authors aimed to evaluate clinical, radiological, and surgical factors associated with posterior fossa tumor resection (PFTR)-related outcomes, including postoperative complications related to dural augmentation (CSF leak and wound infection), persistent hydrocephalus ultimately requiring permanent CSF diversion after PFTR, and 90-day readmission rate.

Methods: Pediatric patients (0-17 years old) undergoing PFTR between 2000 and 2016 at Monroe Carell Jr. Children's Hospital of Vanderbilt University were retrospectively reviewed. Descriptive statistics included the Wilcoxon signed-rank test to compare means that were nonnormally distributed and the chi-square test for categorical variables. Variables that were nominally associated (p < 0.05) with each outcome by univariate analysis were included as covariates in multivariate linear regression models. Statistical significance was set a priori at p < 0.05.

Results: The cohort consisted of 186 patients with a median age at surgery of 6.62 years (range 3.37-11.78 years), 55% male, 83% Caucasian, and average length of follow-up of 3.87 ± 0.25 years. By multivariate logistic regression, the variables primary dural closure (PDC; odds ratio [OR] 8.33, 95% confidence interval [CI] 1.07-100, p = 0.04), pseudomeningocele (OR 7.43, 95% CI 2.23-23.76, p = 0.0007), and hydrocephalus ultimately requiring permanent CSF diversion within 90 days of PFTR (OR 9.25, 95% CI 2.74-31.2, p = 0.0003) were independently associated with CSF leak. PDC versus graft dural closure (GDC; 35% vs 7%, OR 5.88, 95% CI 2.94-50.0, p = 0.03) and hydrocephalus ultimately requiring permanent CSF diversion (OR 3.30, 95% CI 1.07-10.19, p = 0.0007) were associated with wound infection requiring surgical debridement. By multivariate logistic regression, GDC versus PDC (23% vs 37%, OR 0.13, 95% CI 0.02-0.87, p = 0.04) was associated with persistent hydrocephalus ultimately requiring permanent CSF diversion, whereas pre- or post-PFTR ventricular size, placement of peri- or intraoperative extraventricular drain (EVD), and radiation therapy were not. Furthermore, the addition of perioperative EVD placement and dural closure method to a previously validated predictive model of post-PFTR hydrocephalus improved its performance from area under the receiver operating characteristic curve of 0.69 to 0.74. Lastly, the authors found that autologous (vs synthetic) grafts may be protective against persistent hydrocephalus (p = 0.02), but not CSF leak, pseudomeningocele, or wound infection.

Conclusions: These results suggest that GDC, independent of potential confounding factors, may be protective against CSF leak, wound infection, and hydrocephalus in patients undergoing PFTR. Additional studies are warranted to further evaluate clinical and surgical factors impacting PFTR-associated complications.
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http://dx.doi.org/10.3171/2019.9.PEDS1939DOI Listing
November 2019

Cerebrospinal fluid alterations following endoscopic third ventriculostomy with choroid plexus cauterization: a retrospective laboratory analysis of two tertiary care centers.

Childs Nerv Syst 2020 05 28;36(5):1017-1024. Epub 2019 Nov 28.

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: This study sought to determine the previously undescribed cytologic and metabolic alterations that accompany endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC).

Methods: Cerebrospinal fluid (CSF) samples were collected from infant patients with hydrocephalus at the time of index ETV/CPC and again at each reintervention for persistent hydrocephalus. Basic CSF parameters, including glucose, protein, and cell counts, were documented. A multivariable regression model, incorporating known predictors of ETV/CPC outcome, was constructed for each parameter to inform time-dependent normative values.

Results: A total of 187 infants were treated via ETV/CPC for hydrocephalus; initial laboratory values were available for 164 patients. Etiology of hydrocephalus included myelomeningocele (53, 32%), intraventricular hemorrhage of prematurity (43, 26%), aqueductal stenosis (24, 15%), and others (44, 27%). CSF parameters did not differ significantly with age or etiology. Glucose levels initially drop below population average (36 to 32 mg/dL) post-operatively before slowly rising to normal levels (42 mg/dL) by 3 months. Dramatically elevated protein levels post-ETV/CPC (baseline of 59 mg/dL up to roughly 200 mg/dL at 1 month) also normalized over 3 months. No significant changes were appreciated in WBC. RBC counts were very elevated following ETV/CPC and quickly declined over the subsequent month.

Conclusion: CSF glucose and protein deviate significantly from normal ranges following ETV/CPC before normalizing over 3 months. High RBC values immediately post-ETV/CPC decline rapidly. Age at time of procedure and etiology have little influence on common clinical CSF laboratory parameters. Of note, the retrospective study design necessitates ETV/CPC failure, which could introduce bias in the results.
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http://dx.doi.org/10.1007/s00381-019-04415-6DOI Listing
May 2020

Predictors of success for combined endoscopic third ventriculostomy and choroid plexus cauterization in a North American setting: a Hydrocephalus Clinical Research Network study.

J Neurosurg Pediatr 2019 May 31;24(2):128-138. Epub 2019 May 31.

7St. Louis Children's Hospital, St. Louis, Missouri.

Objective: Endoscopic third ventriculostomy combined with choroid plexus cauterization (ETV+CPC) has been adopted by many pediatric neurosurgeons as an alternative to placing shunts in infants with hydrocephalus. However, reported success rates have been highly variable, which may be secondary to patient selection, operative technique, and/or surgeon training. The objective of this prospective multicenter cohort study was to identify independent patient selection, operative technique, or surgical training predictors of ETV+CPC success in infants.

Methods: This was a prospective cohort study nested within the Hydrocephalus Clinical Research Network's (HCRN) Core Data Project (registry). All infants under the age of 2 years who underwent a first ETV+CPC between June 2006 and March 2015 from 8 HCRN centers were included. Each patient had a minimum of 6 months of follow-up unless censored by an ETV+CPC failure. Patient and operative risk factors of failure were examined, as well as formal ETV+CPC training, which was defined as traveling to and working with the experienced surgeons at CURE Children's Hospital of Uganda. ETV+CPC failure was defined as the need for repeat ETV, shunting, or death.

Results: The study contained 191 patients with a primary ETV+CPC conducted by 17 pediatric neurosurgeons within the HCRN. Infants under 6 months corrected age at the time of ETV+CPC represented 79% of the cohort. Myelomeningocele (26%), intraventricular hemorrhage associated with prematurity (24%), and aqueductal stenosis (17%) were the most common etiologies. A total of 115 (60%) of the ETV+CPCs were conducted by surgeons after formal training. Overall, ETV+CPC was successful in 48%, 46%, and 45% of infants at 6 months, 1 year, and 18 months, respectively. Young age (< 1 month) (adjusted hazard ratio [aHR] 1.9, 95% CI 1.0-3.6) and an etiology of post-intraventricular hemorrhage secondary to prematurity (aHR 2.0, 95% CI 1.1-3.6) were the only two independent predictors of ETV+CPC failure. Specific subgroups of ages within etiology categories were identified as having higher ETV+CPC success rates. Although training led to more frequent use of the flexible scope (p < 0.001) and higher rates of complete (> 90%) CPC (p < 0.001), training itself was not independently associated (aHR 1.1, 95% CI 0.7-1.8; p = 0.63) with ETV+CPC success.

Conclusions: This is the largest prospective multicenter North American study to date examining ETV+CPC. Formal ETV+CPC training was not found to be associated with improved procedure outcomes. Specific subgroups of ages within specific hydrocephalus etiologies were identified that may preferentially benefit from ETV+CPC.
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May 2019

Predictors of endoscopic third ventriculostomy ostomy status in patients who experience failure of endoscopic third ventriculostomy with choroid plexus cauterization.

J Neurosurg Pediatr 2019 04;24(1):41-46

1Surgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville.

Objective: At failure of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC), the ETV ostomy may be found to be closed or open. Failure with a closed ostomy may indicate a population that could benefit from evolving techniques to keep the ostomy open and may be candidates for repeat ETV, whereas failure with an open ostomy may be due to persistently abnormal CSF dynamics. This study seeks to identify clinical and radiographic predictors of ostomy status at the time of ETV/CPC failure.

Methods: The authors conducted a multicenter, retrospective cohort study on all pediatric patients with hydrocephalus who failed initial ETV/CPC treatment between January 2013 and October 2016. Failure was defined as the need for repeat ETV or ventriculoperitoneal (VP) shunt placement. Clinical and radiographic data were collected, and ETV ostomy status was determined endoscopically at the subsequent hydrocephalus procedure. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank-sum test, t-test, and Pearson chi-square test where appropriate, as well as multivariate logistic regression.

Results: Of 72 ETV/CPC failures, 28 patients (39%) had open-ostomy failure and 44 (61%) had closed-ostomy failure. Patients with open-ostomy failure were older (median 5.1 weeks corrected age for gestation [interquartile range (IQR) 0.9-15.9 weeks]) than patients with closed-ostomy failure (median 0.2 weeks [IQR -1.3 to 4.5 weeks]), a significant difference by univariate and multivariate regression. Etiologies of hydrocephalus included intraventricular hemorrhage of prematurity (32%), myelomeningocele (29%), congenital communicating (11%), aqueductal stenosis (11%), cyst/tumor (4%), and other causes (12%). A wider baseline third ventricle was associated with open-ostomy failure (median 15.0 mm [IQR 10.3-18.5 mm]) compared to closed-ostomy failure (median 11.7 mm [IQR 8.9-16.5 mm], p = 0.048). Finally, at the time of failure, patients with closed-ostomy failure had enlargement of their ventricles (frontal and occipital horn ratio [FOHR], failure vs baseline, median 0.06 [IQR 0.00-0.11]), while patients with open-ostomy failure had no change in ventricle size (median 0.01 [IQR -0.04 to 0.05], p = 0.018). Previous CSF temporizing procedures, intraoperative bleeding, and time to failure were not associated with ostomy status at ETV/CPC failure.

Conclusions: Older corrected age for gestation, larger baseline third ventricle width, and no change in FOHR were associated with open-ostomy ETV/CPC failure. Future studies are warranted to further define and confirm features that may be predictive of ostomy status at the time of ETV/CPC failure.
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http://dx.doi.org/10.3171/2019.2.PEDS18743DOI Listing
April 2019

Sport-Related Structural Brain Injury in High School Soccer: Epidural Hemorrhage After a "Header".

World Neurosurg 2019 Jul 28;127:20-23. Epub 2019 Mar 28.

Vanderbilt Sports Concussion Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address:

Background: Sports-related structural brain injury (SRSBI) is a rare, but potentially catastrophic, injury. Limited data exist outlining its epidemiology, pathophysiology, and outcomes. We have presented a case of an epidural hematoma (EDH) that occurred during a high school soccer game.

Case Description: A 16-year-old boy had experienced a head-to-ball collision and head-to-head collision with another player. He denied loss of consciousness, endorsed retrograde amnesia, and complained of a minor headache. On the sidelines, he subsequently passed brief orientation and physical exertion tests. However, on returning to play, he experienced blurry vision, along with headache and nausea/vomiting. At the local hospital, he was found to have a 2.6-cm right frontal EDH. After transfer to our institution, increasing somnolence was noted, prompting emergent evacuation of the EDH. His postoperative course was unremarkable, and he was discharged on postoperative day 2. At the 2-week and 3-month follow-up visits, he did not express any complaints or residual deficits and was cleared for full sporting activity.

Conclusions: The present case highlights one of the few SRSBIs that have occurred in soccer. Because of their rarity and severity, a concerted effort should be made to report these cases of SRSBIs regarding the mechanism, postcollision symptoms, and long-term outcomes.
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http://dx.doi.org/10.1016/j.wneu.2019.03.198DOI Listing
July 2019

The cost of hydrocephalus: a cost-effectiveness model for evaluating surgical techniques.

J Neurosurg Pediatr 2018 10;23(1):109-118

1Surgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt.

In BriefThe authors analyzed the costs associated with the three different procedures used to treat hydrocephalus in the pediatric population. They believe this study highlights the importance of patient-specific treatment decisions that are based on etiology and previous intervention. The patient-specific medical characteristics are a driving force in the cost of care.
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http://dx.doi.org/10.3171/2018.6.PEDS17654DOI Listing
October 2018

North American survey on the post-neuroimaging management of children with mild head injuries.

J Neurosurg Pediatr 2018 10;23(2):227-235

Departments of1Neurological Surgery.

OBJECTIVEThere remains uncertainty regarding the appropriate level of care and need for repeating neuroimaging among children with mild traumatic brain injury (mTBI) complicated by intracranial injury (ICI). This study's objective was to investigate physician practice patterns and decision-making processes for these patients in order to identify knowledge gaps and highlight avenues for future investigation.METHODSThe authors surveyed residents, fellows, and attending physicians from the following pediatric specialties: emergency medicine; general surgery; neurosurgery; and critical care. Participants came from 10 institutions in the United States and an email list maintained by the Canadian Neurosurgical Society. The survey asked respondents to indicate management preferences for and experiences with children with mTBI complicated by ICI, focusing on an exemplar clinical vignette of a 7-year-old girl with a Glasgow Coma Scale score of 15 and a 5-mm subdural hematoma without midline shift after a fall down stairs.RESULTSThe response rate was 52% (n = 536). Overall, 326 (61%) respondents indicated they would recommend ICU admission for the child in the vignette. However, only 62 (12%) agreed/strongly agreed that this child was at high risk of neurological decline. Half of respondents (45%; n = 243) indicated they would order a planned follow-up CT (29%; n = 155) or MRI scan (19%; n = 102), though only 64 (12%) agreed/strongly agreed that repeat neuroimaging would influence their management. Common factors that increased the likelihood of ICU admission included presence of a focal neurological deficit (95%; n = 508 endorsed), midline shift (90%; n = 480) or an epidural hematoma (88%; n = 471). However, 42% (n = 225) indicated they would admit all children with mTBI and ICI to the ICU. Notably, 27% (n = 143) of respondents indicated they had seen one or more children with mTBI and intracranial hemorrhage demonstrate a rapid neurological decline when admitted to a general ward in the last year, and 13% (n = 71) had witnessed this outcome at least twice in the past year.CONCLUSIONSMany physicians endorse ICU admission and repeat neuroimaging for pediatric mTBI with ICI, despite uncertainty regarding the clinical utility of those decisions. These results, combined with evidence that existing practice may provide insufficient monitoring to some high-risk children, emphasize the need for validated decision tools to aid the management of these patients.
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http://dx.doi.org/10.3171/2018.7.PEDS18263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717430PMC
October 2018
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