Publications by authors named "Gerald A Grant"

152 Publications

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

Evaluating the Effect of Concussion Education Programs on Intent to Report Concussion in High School Football.

J Athl Train 2021 Jan 6. Epub 2021 Jan 6.

Lecturer and Adjunct Affiliate, Stanford University, School of Education. email:

Context: Concussion underreporting leads to delays in diagnosis and treatment, prolonging recovery time. Athletes' self-report of concussion symptoms therefore reduces risk.

Objective: Evaluate the efficacy of three concussion education programs in improving concussion-reporting intention.

Design: Randomized controlled clinical trial with assessment immediately and one-month after education.

Setting: Three high schools in California.

Patients Or Other Participants: 118 male football players were randomly assigned to receive concussion education via: CrashCourse (CC), Centers for Disease Control (CDC) video educational materials (Vi), or CDC written educational materials (Wr).

Main Outcome Measures: Concussion-reporting intention was assessed at baseline, immediately after education, and at one-month follow-up. Secondary outcomes included concussion knowledge, attitudes, perceived reporting norms, and perceived behavioral control.

Results: Athletes across all educational formats had significant improvement in concussion-reporting intention immediately following education and at one-month follow-up (mean improvement 6.8% and 11.4%, respectively; p<0.001). Similar findings were observed across all education formats in secondary analyses examining knowledge, attitudes, and perceived behavioral control. However, there were significant differences by education and time (p=0.03). On post-hoc analysis, athletes who received CC had increased concussion-reporting intention immediately and at one-month (baseline=4.7, immediate=6.1, one-month=6.0; p=0.007 compared to significant increases only at one-month for CDC-Vi (baseline=4.3, immediate=5.2, one-month=5.8; p=0.001), and no significant improvement for CDC-Wr (p=0.10). Secondary analyses indicated significant differences between CC and both CDC interventions, in concussion knowledge and attitudes, immediately after education and at one-month. There were no significant differences in perceived behavioral control between-interventions or in perceived concussion-reporting norms across or between interventions.

Conclusion: All athletes exhibited improved intent to report concussions, increased concussion knowledge, better concussion attitudes, and more perceived behavioral control, both immediately after education and at one-month follow-up. However, athletes randomized to CC reported greater intent to report concussion, more knowledge, and improved concussion-reporting attitudes, when compared to CDC-Vi and CDC-Wr.

Trial Registry: ClinicalTrials.gov trial ID number is XXX.
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http://dx.doi.org/10.4085/509-20DOI Listing
January 2021

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

Artificial intelligence for automatic cerebral ventricle segmentation and volume calculation: a clinical tool for the evaluation of pediatric hydrocephalus.

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

3Department of Radiology, Stanford University School of Medicine.

Objective: Imaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals.

Methods: The study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as "ground truth" data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software.

Results: Model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan).

Conclusions: The authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.
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http://dx.doi.org/10.3171/2020.6.PEDS20251DOI Listing
December 2020

Contemporaneous evaluation of patient experience, surgical strategy, and seizure outcomes in patients undergoing stereoelectroencephalography or subdural electrode monitoring.

Epilepsia 2021 Jan 25;62(1):74-84. Epub 2020 Nov 25.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

Objective: Intracranial electrographic localization of the seizure onset zone (SOZ) can guide surgical approaches for medically refractory epilepsy patients, especially when the presurgical workup is discordant or functional cortical mapping is required. Minimally invasive stereotactic placement of depth electrodes, stereoelectroencephalography (SEEG), has garnered increasing use, but limited data exist to evaluate its postoperative outcomes in the context of the contemporaneous availability of both SEEG and subdural electrode (SDE) monitoring. We aimed to assess the patient experience, surgical intervention, and seizure outcomes associated with these two epileptic focus mapping techniques during a period of rapid adoption of neuromodulatory and ablative epilepsy treatments.

Methods: We retrospectively reviewed 66 consecutive adult intracranial electrode monitoring cases at our institution between 2014 and 2017. Monitoring was performed with either SEEG (n = 47) or SDEs (n = 19).

Results: Both groups had high rates of SOZ identification (SEEG 91.5%, SDE 88.2%, P = .69). The majority of patients achieved Engel class I (SEEG 29.3%, SDE 35.3%) or II outcomes (SEEG 31.7%, SDE 29.4%) after epilepsy surgery, with no significant difference between groups (P = .79). SEEG patients reported lower median pain scores (P = .03) and required less narcotic pain medication (median = 94.5 vs 594.6 milligram morphine equivalents, P = .0003). Both groups had low rates of symptomatic hemorrhage (SEEG 0%, SDE 5.3%, P = .11). On multivariate logistic regression, undergoing resection or ablation (vs responsive neurostimulation/vagus nerve stimulation) was the only significant independent predictor of a favorable outcome (adjusted odds ratio = 25.4, 95% confidence interval = 3.48-185.7, P = .001).

Significance: Although both SEEG and SDE monitoring result in favorable seizure control, SEEG has the advantage of superior pain control, decreased narcotic usage, and lack of routine need for intensive care unit stay. Despite a heterogenous collection of epileptic semiologies, seizure outcome was associated with the therapeutic surgical modality and not the intracranial monitoring technique. The potential for an improved postoperative experience makes SEEG a promising method for intracranial electrode monitoring.
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http://dx.doi.org/10.1111/epi.16762DOI Listing
January 2021

Deep Learning for Automated Delineation of Pediatric Cerebral Arteries on Pre-operative Brain Magnetic Resonance Imaging.

Front Surg 2020 26;7:517375. Epub 2020 Oct 26.

Department of Radiology, Stanford University, Stanford, CA, United States.

Surgical resection of brain tumors is often limited by adjacent critical structures such as blood vessels. Current intraoperative navigations systems are limited; most are based on two-dimensional (2D) guidance systems that require manual segmentation of any regions of interest (ROI; eloquent structures to avoid or tumor to resect). They additionally require time- and labor-intensive processing for any reconstruction steps. We aimed to develop a deep learning model for real-time fully automated segmentation of the intracranial vessels on preoperative non-angiogram imaging sequences. We identified 48 pediatric patients (10-months to 22-years old) with high resolution (0.5-1 mm axial thickness) isovolumetric, pre-operative T2 magnetic resonance images (MRIs). Twenty-eight patients had anatomically normal brains, and 20 patients had tumors or other lesions near the skull base. Manually segmented intracranial vessels (internal carotid, middle cerebral, anterior cerebral, posterior cerebral, and basilar arteries) served as ground truth labels. Patients were divided into 80/5/15% training/validation/testing sets. A modified Unet convolutional neural network (CNN) architecture implemented with 5 layers was trained to maximize the Dice coefficient, a measure of the correct overlap between the predicted vessels and ground truth labels. The model was able to delineate the intracranial vessels in a held-out test set of normal and tumor MRIs with an overall Dice coefficient of 0.75. While manual segmentation took 1-2 h per patient, model prediction took, on average, 8.3 s per patient. We present a deep learning model that can rapidly and automatically identify the intracranial vessels on pre-operative MRIs in patients with normal vascular anatomy and in patients with intracranial lesions. The methodology developed can be translated to other critical brain structures. This study will serve as a foundation for automated high-resolution ROI segmentation for three-dimensional (3D) modeling and integration into an augmented reality navigation platform.
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http://dx.doi.org/10.3389/fsurg.2020.517375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649258PMC
October 2020

Adverse Events and Bundled Costs after Cranial Neurosurgical Procedures: Validation of the LACE Index Across 40,431 Admissions and Development of the LACE-Cranial Index.

World Neurosurg 2021 Feb 28;146:e431-e451. Epub 2020 Oct 28.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA. Electronic address:

Objective: Anticipating postdischarge complications after neurosurgery remains difficult. The LACE index, based on 4 hospitalization descriptors, stratifies patients by risk of 30-day postdischarge adverse events but has not been validated in a procedure-specific manner in neurosurgery. Our study sought to explore the usefulness of the LACE index in a population undergoing cranial neurosurgery and to develop an enhanced model, LACE-Cranial.

Methods: The OptumClinformatics Database was used to identify cranial neurosurgery admissions (2004-2017). Procedures were grouped as trauma/hematoma/intracranial pressure, open vascular, functional/pain, skull base, tumor, or endovascular. Adverse events were defined as postdischarge death/readmission. LACE-Cranial was developed using a logistic regression framework incorporating an expanded feature set in addition to the original LACE components.

Results: A total of 40,431 admissions were included. Predictions of 30-day readmissions was best for skull base (area under the curve [AUC], 0.636) and tumor (AUC, 0.63) admissions but was generally poor. Predictive ability of 30-day mortality was best for functional/pain admissions (AUC, 0.957) and poorest for trauma/hematoma/intracranial pressure admissions (AUC, 0.613). Across procedure types except for functional/pain, a high-risk LACE score was associated with higher postdischarge bundled payment costs. Incorporating features identified to contribute independent predictive value, the LACE-Cranial model achieved procedure-specific 30-day mortality AUCs ranging from 0.904 to 0.98. Prediction of 30-day and 90-day readmissions was also improved, with tumor and skull base cases achieving 90-day readmission AUCs of 0.718 and 0.717, respectively.

Conclusions: Although the unmodified LACE index shows inconsistent classification performance, the enhanced LACE-Cranial model offers excellent prediction of short-term postdischarge mortality across procedure groups and significantly improved anticipation of short-term postdischarge readmissions.
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http://dx.doi.org/10.1016/j.wneu.2020.10.103DOI Listing
February 2021

Early Effects of COVID-19 Pandemic on Neurosurgical Training in the United States: A Case Volume Analysis of 8 Programs.

World Neurosurg 2021 01 13;145:e202-e208. Epub 2020 Oct 13.

Department of Neurosurgery, University of Louisville, Louisville, Kentucky, USA.

Objective: To determine the impact of the 2019 novel coronavirus disease (COVID-19) pandemic on operative case volume in 8 U.S. neurosurgical residency training programs in early 2020 and to survey these programs regarding training activities during this period.

Methods: A retrospective review was conducted of monthly operative case volumes and types for 8 residency programs for 2019 and January through April 2020. Cases were grouped as elective cranial, elective spine, and nonelective emergent cases. Programs were surveyed regarding residents' perceptions of the impact of COVID-19 on surgical training, didactics, and research participation. Data were analyzed for individual programs and pooled across programs.

Results: Across programs, the 2019 monthly mean ± SD case volume was 211 ± 82; 2020 mean ± SD case volumes for January, February, March, and April were 228 ± 93, 214 ± 84, 180 ± 73, and 107 ± 45. Compared with 2019, March and April 2020 mean cases declined 15% (P = 0.003) and 49% (P = 0.002), respectively. COVID-19 affected surgical case volume for all programs; 75% reported didactics negatively affected, and 90% reported COVID-19 resulted in increased research time. Several neurosurgery residents required COVID-19 testing; however, to our knowledge, only 1 resident from the participating programs tested positive.

Conclusions: This study documents a significant reduction in operative volume in 8 neurosurgery residency training programs in early 2020. During this time, neurosurgery residents engaged in online didactics and research-related activities, reporting increased research productivity. Residency programs should collect data to determine the educational impact of the COVID-19 pandemic on residents' operative case volumes, identify deficiencies, and develop plans to mitigate any effects.
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http://dx.doi.org/10.1016/j.wneu.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550889PMC
January 2021

Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study.

Radiology 2020 Nov 15;297(2):438-446. Epub 2020 Sep 15.

From the Department of Radiology, Division of Neuroimaging and Neurointervention (M.I.), Department of Pathology (J.L.), Department of Radiology, Lucas Center (S.J.H., M.E.M., J.R.), and Department of Neurosurgery, Division of Pediatric Neurosurgery (G.A.G.), Stanford University, Stanford, Calif; Department of Radiology, Pediatric MRI and CT, Division of Pediatric Radiology, Lucile Packard Children's Hospital, Stanford University, 725 Welch Rd, Room G516, Palo Alto, CA 94304 (M.I., N.N.N., S.N., Y.Z., K.W.Y.); and Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT (S.H.C.). From the 2018 RSNA Annual Meeting.

Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec ± 2.09) did not differ between groups (susceptibility, = .21; R2*, = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec ± 2.49) did not differ between the first and last MRI examinations (susceptibility, = .95; R2*, = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020200378DOI Listing
November 2020

Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study.

Radiology 2020 Nov 15;297(2):438-446. Epub 2020 Sep 15.

From the Department of Radiology, Division of Neuroimaging and Neurointervention (M.I.), Department of Pathology (J.L.), Department of Radiology, Lucas Center (S.J.H., M.E.M., J.R.), and Department of Neurosurgery, Division of Pediatric Neurosurgery (G.A.G.), Stanford University, Stanford, Calif; Department of Radiology, Pediatric MRI and CT, Division of Pediatric Radiology, Lucile Packard Children's Hospital, Stanford University, 725 Welch Rd, Room G516, Palo Alto, CA 94304 (M.I., N.N.N., S.N., Y.Z., K.W.Y.); and Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT (S.H.C.). From the 2018 RSNA Annual Meeting.

Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec ± 2.09) did not differ between groups (susceptibility, = .21; R2*, = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec ± 2.49) did not differ between the first and last MRI examinations (susceptibility, = .95; R2*, = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020200378DOI Listing
November 2020

Long-term follow-up of neurosurgical outcomes for adult patients in Uganda with traumatic brain injury.

J Neurosurg 2020 Jul 3:1-11. Epub 2020 Jul 3.

2Department of Neurosurgery, Stanford University, Palo Alto, California.

Objective: Traumatic brain injury (TBI) is a major cause of mortality and morbidity in Uganda and other low- and middle-income countries (LMICs). Due to the difficulty of long-term in-person follow-up, there is a paucity of literature on longitudinal outcomes of TBI in LMICs. Using a scalable phone-centered survey, this study attempted to investigate factors associated with both mortality and quality of life in Ugandan patients with TBI.

Methods: A prospective registry of adult patients with TBI admitted to the neurosurgical ward at Mulago National Referral Hospital was assembled. Long-term follow-up was conducted between 10.4 and 30.5 months after discharge (median 18.6 months). Statistical analyses included univariable and multivariable logistic regression and Cox proportional hazards regression to elucidate factors associated with mortality and long-term recovery.

Results: A total of 1274 adult patients with TBI were included, of whom 302 (23.7%) died as inpatients. Patients who died as inpatients received surgery less frequently (p < 0.001), had more severe TBI at presentation (p < 0.001), were older (p < 0.001), and were more likely to be female (p < 0.0001). Patients presenting with TBI resulting from assault were at reduced risk of inpatient death compared with those presenting with TBI caused by road traffic accidents (OR 0.362, 95% CI 0.128-0.933). Inpatient mortality and postdischarge mortality prior to follow-up were 23.7% and 9%, respectively. Of those discharged, 60.8% were reached through phone interviews. Higher Glasgow Coma Scale score at discharge (continuous HR 0.71, 95% CI 0.53-0.94) was associated with improved long-term survival. Tracheostomy (HR 4.38, 95% CI 1.05-16.7) and older age (continuous HR 1.03, 95% CI 1.009-1.05) were associated with poor long-term outcomes. More than 15% of patients continued to suffer from TBI sequelae years after the initial injury, including seizures (6.1%) and depression (10.0%). Despite more than 60% of patients seeking follow-up healthcare visits, mortality was still 9% among discharged patients, suggesting a need for improved longitudinal care to monitor recovery progress.

Conclusions: Inpatient and postdischarge mortality remain high following admission to Uganda's main tertiary hospital with the diagnosis of TBI. Furthermore, posttraumatic sequelae, including seizures and depression, continue to burden patients years after discharge. Effective scalable solutions, including phone interviews, are needed to elucidate and address factors limiting in-hospital capacity and access to follow-up healthcare.
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http://dx.doi.org/10.3171/2020.4.JNS193092DOI Listing
July 2020

In Reply: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

Neurosurgery 2020 09;87(3):E436-E437

Division of Image Science Department of Radiology University of Calgary Calgary, AB, Canada.

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http://dx.doi.org/10.1093/neuros/nyaa265DOI Listing
September 2020

Recurrence of cavernous malformations after surgery in childhood.

J Neurosurg Pediatr 2020 May 1:1-10. Epub 2020 May 1.

Departments of1Neurosurgery and.

Objective: Cavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.

Methods: Pediatric patients (≤ 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher's exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.

Results: Fifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).

Conclusions: Patients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.
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http://dx.doi.org/10.3171/2020.2.PEDS19543DOI Listing
May 2020

An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci.

Clin Epigenetics 2020 03 14;12(1):46. Epub 2020 Mar 14.

Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Background: Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).

Methods: In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72).

Results: The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10, p = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10, p = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10, p = 0.042).

Conclusions: The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.
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http://dx.doi.org/10.1186/s13148-020-0820-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071645PMC
March 2020

Neurosurgical Randomized Trials in Low- and Middle-Income Countries.

Neurosurgery 2020 09;87(3):476-483

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, United Kingdom.

Background: The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before.

Objective: To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs.

Methods: From January 2003 to July 2016, English-language trials with >5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method.

Results: A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively.

Conclusion: We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated.
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http://dx.doi.org/10.1093/neuros/nyaa049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426187PMC
September 2020

Factors associated with syrinx size in pediatric patients treated for Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

J Neurosurg Pediatr 2020 Mar 6:1-11. Epub 2020 Mar 6.

34Department of Neurological Surgery, Washington University in St. Louis School of Medicine, St. Louis, Missouri.

Objective: Factors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established.

Methods: Using the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length.

Results: The authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16-0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34-1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12-0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02-2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31-3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67-5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate.

Conclusions: These data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.
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http://dx.doi.org/10.3171/2020.1.PEDS19493DOI Listing
March 2020

Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma.

Neurosurgery 2020 05;86(5):E426-E435

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California.

Background: Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.

Objective: To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.

Methods: A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.

Results: Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).

Conclusion: Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.
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http://dx.doi.org/10.1093/neuros/nyaa023DOI Listing
May 2020

Utilization of Novel High-Resolution, MRI-Based Vascular Imaging Modality for Preoperative Stereoelectroencephalography Planning in Children: A Technical Note.

Stereotact Funct Neurosurg 2020 14;98(1):1-7. Epub 2020 Feb 14.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA,

Introduction: Stereoelectroencephalography (SEEG) is a powerful intracranial diagnostic tool that requires accurate imaging for proper electrode trajectory planning to ensure efficacy and maximize patient safety. Computed tomography (CT) angiography and digital subtraction angiography are commonly used, but recent developments in magnetic resonance angiography allow for high-resolution vascular visualization without added risks of radiation. We report on the accuracy of electrode placement under robotic assistance planning utilizing a novel high-resolution magnetic resonance imaging (MRI)-based imaging modality.

Methods: Sixteen pediatric patients between February 2014 and October 2017 underwent SEEG exploration for epileptogenic zone localization. A gadolinium-enhanced 3D T1-weighted spoiled gradient recalled echo sequence with minimum echo time and repetition time was applied for background parenchymal suppression and vascular enhancement. Electrode placement accuracy was determined by analyzing postoperative CT scans laid over preoperative virtual electrode trajectory paths. Entry point, target point, and closest vessel intersection were measured.

Results: For any intersection along the trajectory path, 57 intersected vessels were measured. The mean diameter of an intersected vessel was 1.0343 ± 0.1721 mm, and 21.05% of intersections involved superficial vessels. There were 157 overall intersection + near-miss events. The mean diameter for an involved vessel was 1.0236 ± 0.0928 mm, and superficial vessels were involved in 20.13%. Looking only at final electrode target, 3 intersection events were observed. The mean diameter of an intersected vessel was 1.0125 ± 0.2227 mm. For intersection + near-miss events, 24 were measured. An involved vessel's mean diameter was 1.1028 ± 0.2634 mm. For non-entry point intersections, 45 intersected vessels were measured. The mean diameter for intersected vessels was 0.9526 ± 0.0689 mm. For non-entry point intersections + near misses, 126 events were observed. The mean diameter for involved vessels was 0.9826 ± 0.1008 mm.

Conclusion: We believe this novel sequence allows better identification of superficial and deeper subcortical vessels compared to conventional T1-weighted gadolinium-enhanced MRI.
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http://dx.doi.org/10.1159/000503693DOI Listing
February 2020

Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG).

Epilepsy Behav 2020 03 3;104(Pt A):106905. Epub 2020 Feb 3.

Department of Neurosurgery, Stanford University School of Medicine, United States of America; Division of Pediatric Neurosurgery, Lucile Packard Children's Hospital Stanford, United States of America. Electronic address:

Background: For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips).

Methods: We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures.

Results: Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4 min, P < .001) and length of stay (6.2 versus 12.3 days, P < .001), including days spent in the intensive care unit (ICU; 1.4 versus 5.4 days, P < .001). Stereoelectroencephalography patients tended to report lower pain scores and used significantly less narcotic pain medications (54.2 versus 197.3 mg morphine equivalents, P = .005). No complications were observed. Stereoelectroencephalography and SDE cohorts had comparable inpatient hospital costs (P = .47).

Conclusion: In comparison with subdural electrode placement, SEEG results in a similarly favorable clinical outcome, but with reduced operative time, decreased narcotic usage, and superior pain control without requiring significantly higher costs. The potential for an improved postoperative intracranial electrode monitoring experience makes SEEG especially suitable for pediatric patients.
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http://dx.doi.org/10.1016/j.yebeh.2020.106905DOI Listing
March 2020

Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients.

World Neurosurg 2020 Apr 26;136:e671-e682. Epub 2020 Jan 26.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California. Electronic address:

Background: Ventriculoperitoneal shunts are used to alleviate elevated intracranial pressure due to either hydrocephalus or idiopathic intracranial hypertension; however, shunt failure is a significant neurosurgical problem. Despite increases in intraoperative stereotactic navigation usage over the past decade, its effect on shunt survival remains unclear.

Methods: Shunt-naïve pediatric and adult patients receiving ventriculoperitoneal shunting between 2007 and 2015 were identified in a national administrative database. Multivariable logistic and Cox regressions were used to evaluate factors affecting stereotaxy usage and shunt survival. Matched cohorts were generated by propensity score balancing.

Results: Of 9677 patients identified, 932 received image-guided shunt placement. Total shunt failure rate was not associated with stereotaxy use (20.3% with stereotaxy vs. 19.4% without, P = 0.4602). In the matched setting, shunt survival was not extended by use of image guidance during placement (hazard ratio = 1.134, 95% confidence interval 0.923-1.393). Late shunt failures (defined as failures occurring at least 30 days after shunt placement) caused by infection occurred more frequently in the stereotaxy cohort (hazard ratio = 2.207, 95% confidence interval 1.115-4.366), whereas late shunt failures attributable to mechanical shunt failure were more common in the nonstereotaxy cohort (hazard ratio = 1.406, 95% confidence interval 1.002-1.973).

Conclusions: Our findings suggest stereotaxy use during ventriculoperitoneal shunt placement does not affect shunt survival. Late shunt failures caused by infection occurred more frequently in the stereotaxy cohort, whereas late failures caused by mechanical shunt malfunction were more commonly encountered in the nonstereotaxy cohort.
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http://dx.doi.org/10.1016/j.wneu.2020.01.138DOI Listing
April 2020

Robot-assisted versus manual navigated stereoelectroencephalography in adult medically-refractory epilepsy patients.

Epilepsy Res 2020 01 9;159:106253. Epub 2019 Dec 9.

Division of Pediatric Neurosurgery, Lucile Packard Children's Hospital Stanford, United States. Electronic address:

Objective: Stereoelectroencephalography (SEEG) has experienced a recent growth in adoption for epileptogenic zone (EZ) localization. Advances in robotics have the potential to improve the efficiency and safety of this intracranial seizure monitoring method. We present our institutional experience employing robot-assisted SEEG and compare its operative efficiency, seizure reduction outcomes, and direct hospital costs with SEEG performed without robotic assistance using navigated stereotaxy.

Methods: We retrospectively identified 50 consecutive adult SEEG cases at our institution in this IRB-approved study, of which 25 were navigated with image guidance (hereafter referred to as "navigated") (02/2014-10/2016) and 25 were robot-assisted (09/2016-12/2017). A thorough review of medical/surgical history and operative records with imaging and trajectory plans was done for each patient. Direct inpatient costs related to each technique were compared.

Results: Most common seizure etiologies for patients undergoing navigated and robot-assisted SEEG included non-lesional and benign temporal lesions. Despite having a higher mean number of leads-per-patient (10.2 ± 3.5 versus 7.2 ± 2.6, P = 0.002), robot-assisted cases had a significantly shorter mean operative time than navigated cases (125.5±48.5 versus 173.4±84.3 min, P = 0.02). Comparison of robot-assisted cases over the study interval revealed no significant difference in mean operative time (136.4±51.4 min for the first ten cases versus 109.9±75.8 min for the last ten cases, P = 0.25) and estimated operative time-per-lead (13.4±6.0 min for the first ten cases versus 12.9±7.7 min for the last ten cases, P = 0.86). The mean depth, radial, target, and entry point errors for robot-assisted cases were 2.12±1.89, 1.66±1.58, 3.05±2.02 mm, and 1.39 ± 0.75 mm, respectively. The two techniques resulted in equivalent EZ localization rate (navigated 88 %, robot-assisted 96 %, P = 0.30). Common types of epilepsy surgery performed consisted of implantation of responsive neurostimulation (RNS) device (56 %), resection (19.1 %), and laser ablation (23.8 %) for navigated SEEG. For robot-assisted SEEG, either RNS implantation (68.2 %) or laser ablation (22.7 %) were performed or offered. A majority of navigated and robot-assisted patients who underwent epilepsy surgery achieved either Engel Class I (navigated 36.8 %, robot-assisted 31.6 %) or II (navigated 36.8 %, robot-assisted 15.8 %) outcome with no significant difference between the groups (P = 0.14). Direct hospital cost for robot-assisted SEEG was 10 % higher than non-robotic cases.

Conclusion: This single-institutional study suggests that robotic assistance can enhance efficiency of SEEG without compromising safety or precision when compared to image guidance only. Adoption of this technique with uniform safety and efficacy over a short period of time is feasible with favorable epilepsy outcomes.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.106253DOI Listing
January 2020

Randomized Controlled Trials in Functional Neurosurgery-Association of Device Approval Status and Trial Quality.

Neuromodulation 2020 Jun 11;23(4):496-501. Epub 2019 Dec 11.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

Introduction: Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs.

Methods: We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters.

Results: Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome.

Conclusion: The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality.
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http://dx.doi.org/10.1111/ner.13083DOI Listing
June 2020

Commentary: Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing.

Neurosurgery 2020 08;87(2):E108-E109

Division of Pediatric Neurosurgery, Lucile Packard Children's Hospital Stanford, Palo Alto, California.

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http://dx.doi.org/10.1093/neuros/nyz531DOI Listing
August 2020

Diffusion tensor magnetic resonance imaging of the optic nerves in pediatric hydrocephalus.

Neurosurg Focus 2019 12;47(6):E16

4Division of Pediatric Neuroradiology, Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, Stanford, California.

Objective: While conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus.

Methods: The authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls.

Results: Patients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years).

Conclusions: DTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.
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http://dx.doi.org/10.3171/2019.9.FOCUS19619DOI Listing
December 2019

Cortical stimulation mapping for localization of visual and auditory language in pediatric epilepsy patients.

J Neurosurg Pediatr 2019 Nov 8:1-10. Epub 2019 Nov 8.

4Department of Neurosurgery, Stanford University Hospital, Stanford, California.

Objective: To determine resection margins near eloquent tissue, electrical cortical stimulation (ECS) mapping is often used with visual naming tasks. In recent years, auditory naming tasks have been found to provide a more comprehensive map. Differences in modality-specific language sites have been found in adult patients, but there is a paucity of research on ECS language studies in pediatric patients. The goals of this study were to evaluate word-finding distinctions between visual and auditory modalities and identify which cortical subregions most often contain critical language function in a pediatric population.

Methods: Twenty-one pediatric patients with epilepsy or temporal lobe pathology underwent ECS mapping using visual (n = 21) and auditory (n = 14) tasks. Fisher's exact test was used to determine whether the frequency of errors in the stimulated trials was greater than the patient's baseline error rate for each tested modality and subregion.

Results: While the medial superior temporal gyrus was a common language site for both visual and auditory language (43.8% and 46.2% of patients, respectively), other subregions showed significant differences between modalities, and there was significant variability between patients. Visual language was more likely to be located in the anterior temporal lobe than was auditory language. The pediatric patients exhibited fewer parietal language sites and a larger range of sites overall than did adult patients in previously published studies.

Conclusions: There was no single area critical for language in more than 50% of patients tested in either modality for which more than 1 patient was tested (n > 1), affirming that language function is plastic in the setting of dominant-hemisphere pathology. The high rates of language function throughout the left frontal, temporal, and anterior parietal regions with few areas of overlap between modalities suggest that ECS mapping with both visual and auditory testing is necessary to obtain a comprehensive language map prior to epileptic focus or tumor resection.
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http://dx.doi.org/10.3171/2019.8.PEDS1922DOI Listing
November 2019

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury.

J Neurotrauma 2020 01 8;37(2):347-356. Epub 2019 Nov 8.

Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.
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http://dx.doi.org/10.1089/neu.2019.6483DOI Listing
January 2020

The authors reply.

Pediatr Crit Care Med 2019 11;20(11):1105-1107

Department of Critical Care Medicine, Anesthesiology, Pediatrics, Bioengineering, and Clinical and Translational Science, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA Department of Neurology and Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR Pediatric Neurosurgery, BARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ Department of Neurological Surgery, Oregon Health & Science University, Portland, OR Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR Critical Care Medicine, Children's National Medical Center, Washington, DC Pediatrics, University of Utah, Salt Lake City, UT Department of Neurosurgery, Stanford University, Stanford, CA Department of Pediatrics, British Columbia's Children's Hospital, Clinical Investigator, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada School of Nursing/School of Medicine, Department of Pediatrics, Division of Pediatric Critical Care Medicine, Duke University, Durham, NC Anesthesiology & Pain Medicine, Pediatrics, Harborview Injury Prevention and Research Center (HIPRC), University of Washington, Seattle, WA Division of Pediatric Neurology, University of Washington, Seattle Children's Hospital, Seattle, WA.

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http://dx.doi.org/10.1097/PCC.0000000000002095DOI Listing
November 2019

Risks, costs, and outcomes of cerebrospinal fluid leaks after pediatric skull fractures: a MarketScan analysis between 2007 and 2015.

Neurosurg Focus 2019 11;47(5):E10

Objective: Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes.

Methods: The authors queried the MarketScan database (2007-2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs.

Results: The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non-CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6-13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2-44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7-5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5-4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001).

Conclusions: The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.
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http://dx.doi.org/10.3171/2019.8.FOCUS19543DOI Listing
November 2019

Outcomes in children undergoing posterior fossa decompression and duraplasty with and without tonsillar reduction for Chiari malformation type I and syringomyelia: a pilot prospective multicenter cohort study.

J Neurosurg Pediatr 2019 Oct 18:1-9. Epub 2019 Oct 18.

1Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.

Objective: Despite significant advances in diagnostic and surgical techniques, the surgical management of Chiari malformation type I (CM-I) with associated syringomyelia remains controversial, and the type of surgery performed is surgeon dependent. This study's goal was to determine the feasibility of a prospective, multicenter, cohort study for CM-I/syringomyelia patients and to provide pilot data that compare posterior fossa decompression and duraplasty (PFDD) with and without tonsillar reduction.

Methods: Participating centers prospectively enrolled children suffering from both CM-I and syringomyelia who were scheduled to undergo surgical decompression. Clinical data were entered into a database preoperatively and at 1-2 weeks, 3-6 months, and 1 year postoperatively. MR images were evaluated by 3 independent, blinded teams of neurosurgeons and neuroradiologists. The primary endpoint was improvement or resolution of the syrinx.

Results: Eight clinical sites were chosen based on the results of a published questionnaire intended to remove geographic and surgeon bias. Data from 68 patients were analyzed after exclusions, and complete clinical and imaging records were obtained for 55 and 58 individuals, respectively. There was strong agreement among the 3 radiology teams, and there was no difference in patient demographics among sites, surgeons, or surgery types. Tonsillar reduction was not associated with > 50% syrinx improvement (RR = 1.22, p = 0.39) or any syrinx improvement (RR = 1.00, p = 0.99). There were no surgical complications.

Conclusions: This study demonstrated the feasibility of a prospective, multicenter surgical trial in CM-I/syringomyelia and provides pilot data indicating no discernible difference in 1-year outcomes between PFDD with and without tonsillar reduction, with power calculations for larger future studies. In addition, the study revealed important technical factors to consider when setting up future trials. The long-term sequelae of tonsillar reduction have not been addressed and would be an important consideration in future investigations.
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http://dx.doi.org/10.3171/2019.8.PEDS19154DOI Listing
October 2019

Commentary: Characteristics and Long-Term Outcome of 20 Children With Intramedullary Spinal Cord Cavernous Malformations.

Neurosurgery 2020 06;86(6):E524-E525

Lucile Packard Children's Hospital Stanford, Division of Pediatric Neurosurgery, Palo Alto, California.

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http://dx.doi.org/10.1093/neuros/nyz431DOI Listing
June 2020