Publications by authors named "Paul Klimo"

214 Publications

Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial.

Neurooncol Adv 2021 Jan-Dec;3(1):vdaa168. Epub 2020 Dec 15.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Choroid plexus carcinoma (CPC) is a rare and aggressive tumor of infancy without a clear treatment strategy. This study describes the outcomes of children with CPC treated on the multi-institutional phase 2 SJYC07 trial and reports on the significance of clinical and molecular characteristics.

Methods: Eligible children <3 years-old with CPC were postoperatively stratified to intermediate-risk (IR) stratum if disease was localized or high-risk (HR) stratum, if metastatic. All received high-dose methotrexate-containing induction chemotherapy. IR-stratum patients received focal irradiation as consolidation whereas HR-stratum patients received additional chemotherapy. Consolidation was followed by oral antiangiogenic maintenance regimen. Survival rates and potential prognostic factors were analyzed.

Results: Thirteen patients (median age: 1.41 years, range: 0.21-2.93) were enrolled; 5 IR, 8 HR. Gross-total resection or near-total resection was achieved in ten patients and subtotal resection in 3. Seven patients had -mutant tumors, including 4 who were germline carriers. Five patients experienced progression and died of disease; 8 (including 5 HR) are alive without progression. The 5-year progression-free survival (PFS) and overall survival rates were 61.5 ± 13.5% and 68.4 ± 13.1%. Patients with -wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for -mutant tumors ( = .012). Extent of resection, metastatic status, and use of radiation therapy were not significantly associated with survival.

Conclusions: Non-myeloablative high-dose methotrexate-containing therapy with maximal surgical resection resulted in long-term PFS in more than half of patients with CPC. mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials.
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http://dx.doi.org/10.1093/noajnl/vdaa168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813199PMC
December 2020

Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma.

J Clin Oncol 2021 Mar 27;39(7):807-821. Epub 2021 Jan 27.

Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN.

Purpose: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors.

Methods: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing.

Results: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving , , and . Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms.

Conclusion: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.
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http://dx.doi.org/10.1200/JCO.20.01359DOI Listing
March 2021

Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03).

J Clin Oncol 2021 Mar 6;39(7):822-835. Epub 2021 Jan 6.

Division of Brain Tumor Research, Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN.

Purpose: SJMB03 (ClinicalTrials.gov identifier: NCT00085202) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants and genetic alterations in medulloblastoma.

Patients And Methods: Patients 3-21 years old were stratified into average-risk and high-risk treatment groups based on metastatic status and extent of resection. Medulloblastomas were molecularly classified into subgroups (Wingless [WNT], Sonic Hedgehog [SHH], group 3, and group 4) and subtypes based on DNA methylation profiles and overlaid with gene mutations from next-generation sequencing. Coprimary study end points were (1) to assess the relationship between ERBB2 protein expression in tumors and progression-free survival (PFS), and (2) to estimate the frequency of mutations associated with WNT and SHH tumors. Clinical and molecular risk factors were evaluated, and the most robust were used to model new risk-classification categories.

Results: Three hundred thirty eligible patients with medulloblastoma were enrolled. Five-year PFS was 83.2% (95% CI, 78.4 to 88.2) for average-risk patients (n = 227) and 58.7% (95% CI, 49.8 to 69.1) for high-risk patients (n = 103). No association was found between ERBB2 status and PFS in the overall cohort ( = .74) or when patients were stratified by clinical risk ( = .71). Mutations in (96%), (37%), and (24%) were most common in WNT tumors and (38%), (21%), and (19%) in SHH tumors. Methylome profiling classified 53 WNT (17.4%), 48 SHH (15.7%), 65 group 3 (21.3%), and 139 group 4 (45.6%) tumors. A comprehensive clinicomolecular risk factor analysis identified three low-risk groups (WNT, low-risk SHH, and low-risk combined groups 3 and 4) with excellent (5-year PFS > 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS < 60%).

Conclusion: These results establish a new risk stratification for future medulloblastoma trials.
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http://dx.doi.org/10.1200/JCO.20.01372DOI Listing
March 2021

Predictors of an Extended Length of Stay following an Elective Craniotomy in Children and Young Adults.

Pediatr Neurosurg 2020 23;55(5):259-267. Epub 2020 Oct 23.

Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.

Background: Length of stay (LOS) is now a generally accepted clinical metric within the USA. An extended LOS following an elective craniotomy can significantly impact overall costs. Few studies have evaluated predictors of an extended LOS in pediatric neurosurgical patients.

Objective: The aim of the study was to determine predictors of an extended hospital LOS following an elective craniotomy in children and young adults.

Methods: All pediatric patients and young adults undergoing an elective craniotomy between January 1, 2010, and April 1, 2019, were retrospectively identified using a prospectively maintained database. Demographic, clinical, radiological, and surgical data were collected. The primary outcome was extended LOS, defined as a postsurgical stay greater than 7 days. Bivariate and multivariable analyses were performed.

Results: A total of 1,498 patients underwent 1,720 elective craniotomies during the study period over the course of 1,698 hospitalizations with a median LOS of 4 days (interquartile range 3-6 days). Of these encounters, 218 (12.8%) had a prolonged LOS. Multivariable analysis demonstrated that non-Caucasian race (OR = 1.9 [African American]; OR = 1.6 [other]), the presence of an existing shunt (OR = 1.8), the type of craniotomy (OR = 0.3 [vascular relative to Chiari]), and the presence of a postoperative complication (OR = 14.7) were associated with an extended LOS.

Conclusions: Inherent and modifiable factors predict a hospital stay of more than a week in children and young adults undergoing an elective craniotomy.
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http://dx.doi.org/10.1159/000511090DOI Listing
October 2020

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

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

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

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

The economic value of an on-call neurosurgical resident physician.

J Neurosurg 2020 Sep 11:1-7. Epub 2020 Sep 11.

1Department of Neurosurgery, University of Tennessee Health Sciences Center, Memphis.

Objective: The cost of training neurosurgical residents is especially high considering the duration of training and the technical nature of the specialty. Despite these costs, on-call residents are a source of significant economic value, through both indirectly and directly supervised activities. The authors sought to identify the economic value of on-call services provided by neurosurgical residents.

Methods: A personal call log kept by a single junior neurosurgical resident over a 2-year period was used to obtain the total number of consultations, admissions, and procedures. Current Procedural Terminology (CPT) codes were used to estimate the resident's on-call economic value.

Results: A single on-call neurosurgical resident at the authors' institution produced 8172 work relative value units (wRVUs) over the study period from indirectly and directly supervised activities. Indirectly supervised procedures produced 7052 wRVUs, and directly supervised activities using the CPT modifier 80 yielded an additional 1120 wRVUs. Using the assistant surgeon billing rate for directly supervised activities and the Medical Group Management Association nationwide median neurosurgery reimbursement rate, the on-call activities of a single resident generated a theoretical billing value of $689,514 over the 2-year period, or $344,757 annually. As a program, the on-call residents collectively produced 39,550 wRVUs over the study period, or 19,775 wRVUs annually, which equates to potential reimbursements of $1,668,386 annually.

Conclusions: Neurosurgery residents at the authors' institution theoretically produce enough economic value exclusively from on-call activities to far exceed the cost of their education. This information could be used to more precisely estimate the true overall cost of neurosurgical training and determine future graduate medical education funding.
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http://dx.doi.org/10.3171/2020.3.JNS193454DOI Listing
September 2020

Neurosurgical Operative Videos: An Analysis of an Increasingly Popular Educational Resource.

World Neurosurg 2020 Dec 2;144:e428-e437. Epub 2020 Sep 2.

Division of Neurosurgery, Connecticut Children's, Hartford, Connecticut, USA; Department of Surgery, UConn School of Medicine, Farmington, Connecticut, USA. Electronic address:

Objective: Surgical education has increasingly relied on electronic learning. In particular, online operative videos have become a core resource within neurosurgery. We analyze the forums for neurosurgical operative videos.

Methods: Operative videos from 5 sources were reviewed: 1) the NEUROSURGERY Journal YouTube channel; 2) the American Association of Neurological Surgeons Neurosurgery YouTube channel; 3) The Neurosurgical Atlas Operative Video Cases; 4) Operative Neurosurgery; and 5) Neurosurgical Focus: Video. Title, year of publication, senior author, institution, country, and subspecialty were documented for each video.

Results: A total of 1233 videos showing 1247 surgeries were identified. Ten videos included >1 surgery; of those, there was a median of 2 surgeries (interquartile range, 2.0-2.5) per video. The most frequently represented subspecialties included vascular (48.3%), tumor (35.2%), and skull base surgery (27.5%), with almost 40% of videos showing >1 category. Videos were submitted by investigators from 28 countries, but 82.1% of the videos originated in the United States.

Conclusions: Neurosurgical operative videos have become increasingly common through a variety of online platforms. Future efforts may benefit from collecting videos from underrepresented regions and subspecialties, providing long-term follow-up data and showing techniques for managing complications.
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http://dx.doi.org/10.1016/j.wneu.2020.08.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462871PMC
December 2020

Dissecting the Financial Relationship between Industry and Academic Neurosurgery.

Neurosurgery 2020 Aug 11. Epub 2020 Aug 11.

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee.

Background: Established by the Centers for Medicare and Medicaid Services (CMS), the Open Payments Database (OPD) has reported industry payments to physicians since August 2013.

Objective: To evaluate the frequency, type, and value of payments received by academic neurosurgeons in the United States over a 5-yr period (2014-2018).

Methods: The OPD was queried for attending neurosurgeons from all neurosurgical training programs in the United States (n = 116). Information from the OPD was analyzed for the entire cohort as well as for comparative subgroup analyses, such as career stage, subspecialty, and geographic location.

Results: Of all identified neurosurgeons, 1509 (95.0%) received some payment from industry between 2014 and 2018 for a total of 106 171 payments totaling $266 407 458.33. A bimodal distribution was observed for payment number and total value: 0 to 9 (n = 438) vs > 50 (n = 563) and 0-$1000 (n = 418) vs >$10 000 (n = 653), respectively. Royalty/License was the most common type of payment overall (59.6%; $158 723 550.57). The median number (40) and value ($8958.95) of payments were highest for mid-career surgeons. The South-Central region received the most money ($117 970 036.39) while New England received the greatest number of payments (29 423). Spine surgeons had the greatest median number (60) and dollar value ($20 551.27) of payments, while pediatric neurosurgeons received the least (8; $1108.29). Male neurosurgeons received a greater number (31) and value ($6395.80) of payments than their female counterparts (11, $1643.72).

Conclusion: From 2014 to 2018, payments to academic neurosurgeons have increased in number and value. Dollars received were dependent on geography, career stage, subspecialty and gender.
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http://dx.doi.org/10.1093/neuros/nyaa257DOI Listing
August 2020

Safety and efficacy of brainstem biopsy in children and young adults.

J Neurosurg Pediatr 2020 Jul 31:1-11. Epub 2020 Jul 31.

3Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee.

Objective: Biopsies of brainstem lesions are performed to establish a diagnosis in the setting of an atypical clinical or radiological presentation, or to facilitate molecular studies. A better understanding of the safety and diagnostic yield of brainstem biopsies would help guide appropriate patient selection.

Methods: All patients who underwent biopsy of a brainstem lesion during the period from January 2011 to June 2019 were reviewed. Demographic, radiological, surgical, and outcome data were collected.

Results: A total of 58 patients underwent 65 brainstem biopsies during the study period. Overall, the median age was 7.6 years (IQR 3.9-14.2 years). Twenty-two of the 65 biopsies (34%) were open, 42 (65%) were stereotactic, and 1 was endoscopic. In 3 cases (5%), a ventriculoperitoneal shunt was placed, and in 9 cases (14%), a posterior fossa decompression was performed during the same operative session as the biopsy. An intraoperative MRI (iMRI) was performed in 28 cases (43%). In 3 of these cases (11%), the biopsy was off target and additional samples were obtained during the same procedure. New neurological deficits were noted in 5 cases (8%), including sensory deficits, ophthalmoparesis/nystagmus, facial weakness, and hearing loss; these deficits persisted in 2 cases and were transient in 3 cases. A pseudomeningocele occurred in 1 patient; no patients developed a CSF leak or infection. In 8 cases (13%) an additional procedure was needed to obtain a diagnosis.

Conclusions: Brainstem biopsies are safe and effective. Target selection and approach should be a collaborative effort. iMRI can be used to assess biopsy accuracy in real time, thereby allowing any adjustment if necessary.
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http://dx.doi.org/10.3171/2020.4.PEDS2092DOI Listing
July 2020

Patient-derived orthotopic xenografts of pediatric brain tumors: a St. Jude resource.

Acta Neuropathol 2020 08 10;140(2):209-225. Epub 2020 Jun 10.

Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Pediatric brain tumors are the leading cause of cancer-related death in children. Patient-derived orthotopic xenografts (PDOX) of childhood brain tumors have recently emerged as a biologically faithful vehicle for testing novel and more effective therapies. Herein, we provide the histopathological and molecular analysis of 37 novel PDOX models generated from pediatric brain tumor patients treated at St. Jude Children's Research Hospital. Using a combination of histopathology, whole-genome and whole-exome sequencing, RNA-sequencing, and DNA methylation arrays, we demonstrate the overall fidelity and inter-tumoral molecular heterogeneity of pediatric brain tumor PDOX models. These models represent frequent as well as rare childhood brain tumor entities, including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor, and embryonal tumor with multi-layer rosettes. PDOX models will be valuable platforms for evaluating novel therapies and conducting pre-clinical trials to accelerate progress in the treatment of brain tumors in children. All described PDOX models and associated datasets can be explored using an interactive web-based portal and will be made freely available to the research community upon request.
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http://dx.doi.org/10.1007/s00401-020-02171-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360541PMC
August 2020

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

Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG.

Acta Neuropathol Commun 2020 04 23;8(1):57. Epub 2020 Apr 23.

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Diffuse intrinsic pontine glioma (DIPG) is most commonly diagnosed based on imaging criteria, with biopsy often reserved for pontine tumors with imaging features not typical for DIPG (atypical DIPG, 'aDIPG'). The histopathologic and molecular spectra of the clinical entity aDIPG remain to be studied systematically. In this study, thirty-three patients with newly diagnosed pontine-centered tumors with imaging inconsistent with DIPG for whom a pathologic diagnosis was subsequently obtained were included. Neoplasms were characterized by routine histology, immunohistochemistry, interphase fluorescence in situ hybridization, Sanger and next-generation DNA/RNA sequencing, and genome-wide DNA methylome profiling. Clinicopathologic features and survival outcomes were analyzed and compared to those of a contemporary cohort with imaging features consistent with DIPG (typical DIPG, 'tDIPG'). Blinded retrospective neuroimaging review assessed the consistency of the initial imaging-based diagnosis and correlation with histopathology. WHO grade II-IV infiltrating gliomas were observed in 54.6% of the cases; the remaining were low-grade gliomas/glioneuronal tumors or CNS embryonal tumors. Histone H3 K27M mutation, identified in 36% of the cases, was the major prognostic determinant. H3 K27M-mutant aDIPG and H3 K27M-mutant tDIPG had similar methylome profiles but clustered separately from diffuse midline gliomas of the diencephalon and spinal cord. In the aDIPG cohort, clinicoradiographic features did not differ by H3 status, yet significant differences in clinical and imaging features were observed between aDIPG without H3 K27M mutation and tDIPG. Neuroimaging review revealed discordance between the classification of aDIPG and tDIPG and did not correlate with the histology of glial/glioneuronal tumors or tumor grade. One patient (3.1%) developed persistent neurologic deficits after surgery; there were no surgery-related deaths. Our study demonstrates that surgical sampling of aDIPG is well-tolerated and provides significant diagnostic, therapeutic, and prognostic implications, and that neuroimaging alone is insufficient to distinguish aDIPG from tDIPG. H3 K27M-mutant aDIPG is epigenetically and clinically similar to H3 K27M-mutant tDIPG.
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http://dx.doi.org/10.1186/s40478-020-00930-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181591PMC
April 2020

Treatment-related calvarial lesions in pediatric brain tumor survivors.

Pediatr Blood Cancer 2020 06 14;67(6):e28189. Epub 2020 Apr 14.

Department of Neurosurgery, LeBonheur Children's Hospital, Memphis, Tennessee.

Background: Despite improved survival, many pediatric brain tumor survivors receiving radiation therapy (RT) experience late effects.

Procedure: To study calvarial lesions in this population, we retrospectively reviewed records of patients undergoing neurosurgical evaluation for calvarial bone lesions detected in posttreatment follow-up imaging at St. Jude Children's Research Hospital. Primary tumor diagnosis, treatment, imaging, surgical intervention, and histopathology from patients with radiographic evidence of lesions followed for ≥2 years post-RT were studied.

Results: For 17 patients with 18 index lesions, median time to lesion manifestation was 2.34 years. Medulloblastoma patients developed lesions at a shorter interval from RT than ependymoma patients (P = .05). Twelve of 14 lesions requiring surgery were benign fibro-osseous or sclerotic. Two malignant lesions distinct from the primary tumor had genetic predisposition to malignancy.

Conclusion: Most calvarial lesions arising post-RT are benign and fibro-osseous. Serial imaging is recommended, and high index of suspicion for malignant lesions is warranted for patients genetically predisposed to cancer.
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http://dx.doi.org/10.1002/pbc.28189DOI Listing
June 2020

What Variables Correlate With Different Clinical Outcomes of Abusive Head Injury?

Neurosurgery 2020 09;87(4):803-810

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee.

Background: The spectrum of injury severity for abusive head trauma (AHT) severity is broad, but outcomes are unequivocally worse than accidental trauma. There are few publications that analyze different outcomes of AHT.

Objective: To determine variables associated with different outcomes of AHT.

Methods: Patients were identified using our AHT database. Three different, but not mutually exclusive, outcomes of AHT were modeled: (1) death or hemispheric stroke (diffuse loss of grey-white differentiation); (2) stroke(s) of any size; and (3) need for a neurosurgical operation. Demographic and clinical variables were collected and correlations to the 3 outcomes of interest were identified using bivariate and multivariable analysis.

Results: From January 2009 to December 2017, 305 children were identified through a prospectively maintained AHT database. These children were typically male (60%), African American (54%), and had public or no insurance (90%). A total of 29 children (9.5%) died or suffered a massive hemispheric stroke, 57 (18.7%) required a neurosurgical operation, and 91 (29.8%) sustained 1 or more stroke. Death or hemispheric stroke was statistically associated with the pupillary exam (odds ratio [OR] = 45.7) and admission international normalized ratio (INR) (OR = 17.3); stroke was associated with the pupillary exam (OR = 13.2), seizures (OR = 14.8), admission hematocrit (OR = 0.92), and INR (9.4), and need for surgery was associated with seizures (OR = 8.6).

Conclusion: We have identified several demographic and clinical variables that correlate with 3 clinically applicable outcomes of abusive head injury.
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http://dx.doi.org/10.1093/neuros/nyaa058DOI Listing
September 2020

Innovation, Royalties, and Introduction of the Patent Hirsch Index within U.S. Academic Neurosurgery.

World Neurosurg 2020 05 5;137:e395-e405. Epub 2020 Feb 5.

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA; Le Bonheur Children's Hospital, Memphis, Tennessee, USA; Semmes Murphey Clinic, Memphis, Tennessee, USA. Electronic address:

Background: Historically, practicing neurosurgeons have been key drivers of neurosurgical innovation. We sought to describe the patents held by U.S. academic neurosurgeons and to explore the relationship between patents and royalties received.

Methods: The Centers for Medicare and Medicaid CMS Open Payments Data was used to identify academic neurosurgeons who had received royalties and royalty amounts during a 5-year period (2013-2017). Online patent databases were used to gather patent details. Patent citations and 5-year individual and departmental patent Hirsch (h)-indexes were calculated. Royalties were correlated with the number of patents, patent citations, and patent h-index.

Results: We found that 119 academic neurosurgeons (7.8%) from 57 U.S. teaching programs (48.3%) had received royalty payments; 72 (60.5%) had published 648 patents. All surgeons were men, with approximately one half in the "late" stages of their career (45.3%) and subspecializing in spinal surgery (50.4%). The patented products or devices were most commonly used for spinal surgery (72.1%), with 2010-2019 the most productive period (n = 455; 70.2%). The median number of citations per patent was 32 (range, 0-620), with 33% having ≥100 citations. The highest individual and institutional patent h-index was 95; 25 (34.7%) neurosurgeons had a patent h-index of ≥5. The median total royalty payment per individual neurosurgeon was $111,011 (range, $58.05-$76,715,750.34). Royalties were correlated with the number of patents (Spearman r = 0.37; P ≤ 0.001), citations (Spearman r, 0.38; P ≤ 0.001), and inventor h-index (Spearman r = 0.38; P ≤ 0.001).

Conclusions: Few U.S. academic neurosurgeons (7.8%) receive royalties and hold patents (4.7%), with an even smaller select group having a patent h-index of ≥5 (1.6%).
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http://dx.doi.org/10.1016/j.wneu.2020.01.223DOI Listing
May 2020

A hospital-based analysis of pseudomeningoceles after elective craniotomy in children: what predicts need for intervention?

J Neurosurg Pediatr 2020 Jan 31:1-8. Epub 2020 Jan 31.

6Department of Neurosurgery, University of Tennessee Health Science Center, Memphis.

Objective: In pediatric patients, the development of a postoperative pseudomeningocele after an elective craniotomy is not unusual. Most will resolve with time, but some may require intervention. In this study, the authors analyzed patients who required intervention for a postoperative pseudomeningocele following an elective craniotomy or craniectomy and identified factors associated with the need for intervention.

Methods: An institutional operative database of elective craniotomies and craniectomies was queried to identify all surgeries associated with development of a postoperative pseudomeningocele from January 1, 2010, to December 31, 2017. Demographic and surgical data were collected, as were details regarding postoperative events and interventions during either the initial admission or upon readmission. A bivariate analysis was performed to compare patients who underwent observation with those who required intervention.

Results: Following 1648 elective craniotomies or craniectomies, 84 (5.1%) clinically significant pseudomeningoceles were identified in 82 unique patients. Of these, 58 (69%) of the pseudomeningoceles were diagnosed during the index admission (8 of which persisted and resulted in readmission), and 26 (31%) were diagnosed upon readmission. Forty-nine patients (59.8% of those with a pseudomeningocele) required one or more interventions, such as lumbar puncture(s), lumbar drain placement, wound exploration, or shunt placement or revision. Only race (p < 0.01) and duraplasty (p = 0.03, OR 3.0) were associated with the need for pseudomeningocele treatment.

Conclusions: Clinically relevant pseudomeningoceles developed in 5% of patients undergoing an elective craniotomy, with 60% of these pseudomeningoceles needing some form of intervention. The need for intervention was associated with race and whether a duraplasty was performed.
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http://dx.doi.org/10.3171/2019.11.PEDS19227DOI Listing
January 2020

Commentary: The Clinical Experience of a Junior Resident in Pediatric Neurosurgery and Introduction of the Resident Experience Score.

Neurosurgery 2020 05;86(5):E447-E454

Department of Neurosurgery, University of Tennessee Health Sciences Center, Memphis, Tennessee.

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http://dx.doi.org/10.1093/neuros/nyz565DOI Listing
May 2020

Correction to: Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials.

Acta Neuropathol 2020 02;139(2):273-275

Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.

The original version of this article unfortunately contained a typesetting error in Fig 3c. The corrected Fig. 3 is given in the following page.
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http://dx.doi.org/10.1007/s00401-019-02115-8DOI Listing
February 2020

Commentary: Antibiotic or Silver Versus Standard Ventriculoperitoneal Shunts (BASICS): A Multicentre, Single-Blinded, Randomised Trial and Economic Evaluation.

Neurosurgery 2020 06;86(6):E568-E569

Department of Neurosurgery, The Ohio State University, Columbus, Ohio.

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June 2020

Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials.

Acta Neuropathol 2020 02 4;139(2):259-271. Epub 2019 Dec 4.

Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.

Pineoblastoma is a rare embryonal tumor of childhood that is conventionally treated with high-dose craniospinal irradiation (CSI). Multi-dimensional molecular evaluation of pineoblastoma and associated intertumoral heterogeneity is lacking. Herein, we report outcomes and molecular features of children with pineoblastoma from two multi-center, risk-adapted trials (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. The clinical cohort consisted of 58 patients with histologically diagnosed pineoblastoma (SJMB03 = 30, SJYC07 = 12, non-protocol = 16, including 12 managed with SJMB03-like therapy). The SJMB03 protocol comprised risk-adapted CSI (average-risk = 23.4 Gy, high-risk = 36 Gy) with radiation boost to the primary site and adjuvant chemotherapy. The SJYC07 protocol consisted of induction chemotherapy, consolidation with focal radiation (intermediate-risk) or chemotherapy (high-risk), and metronomic maintenance therapy. The molecular cohort comprised 43 pineal parenchymal tumors profiled by DNA methylation array (n = 43), whole-exome sequencing (n = 26), and RNA-sequencing (n = 16). Respective 5-year progression-free survival rates for patients with average-risk or high-risk disease on SJMB03 or SJMB03-like therapy were 100% and 56.5 ± 10.3% (P = 0.007); respective 2-year progression-free survival rates for those with intermediate-risk or high-risk disease on SJYC07 were 14.3 ± 13.2% and 0% (P = 0.375). Of patients with average-risk disease treated with SJMB03/SJMB03-like therapy, 17/18 survived without progression. DNA-methylation analysis revealed four clinically relevant pineoblastoma subgroups: PB-A, PB-B, PB-B-like, and PB-FOXR2. Pineoblastoma subgroups differed in age at diagnosis, propensity for metastasis, cytogenetics, and clinical outcomes. Alterations in the miRNA-processing pathway genes DICER1, DROSHA, and DGCR8 were recurrent and mutually exclusive in PB-B and PB-B-like subgroups; PB-FOXR2 samples universally overexpressed the FOXR2 proto-oncogene. Our findings suggest superior outcome amongst older children with average-risk pineoblastoma treated with reduced-dose CSI. The identification of biologically and clinically distinct pineoblastoma subgroups warrants consideration of future molecularly-driven treatment protocols for this rare pediatric brain tumor entity.
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http://dx.doi.org/10.1007/s00401-019-02106-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065912PMC
February 2020

Converting Pediatric Patients and Young Adults From a Shunt to a Third Ventriculostomy: A Multicenter Evaluation.

Neurosurgery 2020 08;87(2):285-293

Department of Neurosurgery, The University of Tennessee Health Science Center, The University of Tennessee, Memphis, Tennessee.

Background: Endoscopic third ventriculostomy (ETV) is an effective primary treatment for certain forms of hydrocephalus. However, its use in children with an existing shunt is less well known.

Objective: To report a multicenter experience in attempting to convert patients from shunt dependence to a third ventriculostomy and to determine predictors of success.

Methods: Three participating centers provided retrospectively collected information on patients with an attempted conversion from a shunt to an ETV between December 1, 2008, and April 1, 2018. Demographic, clinical, and radiological data were recorded. Success was defined as shunt independence at the last follow-up.

Results: Eighty patients with an existing ventricular shunt underwent an ETV. The median age at the time of the index ETV was 9.9 yr, and 44 (55%) patients were male. The overall success rate was 64% (51/80), with a median duration of follow-up of 2.0 yr (range, 0.1-9.4 yr). Four patients required a successful repeat ETV at a median of 1.7 yr (range, 0.1-5.7 yr) following the index ETV. Only age was predictive of ETV failure on multivariate analysis (odds ratio 0.86 [95% CI 0.78-0.94], P = .005). No patient less than 6 mo of age underwent an ETV, and of the 5 patients between 6 and 12 mo of age, 4 failed.

Conclusion: Although not every shunted patient will be a candidate for an ETV, nor will they be successfully converted, an ETV should at least be considered in every child who presents with a shunt malfunction or who has an externalized shunt.
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August 2020

A Survey of Neurological Surgery Residency Program Mentorship Practices Compared to Accreditation Council for Graduate Medical Education Resident Outcome Data.

Neurosurgery 2020 10;87(5):E566-E572

Review Committee for Neurological Surgery, Accreditation Council for Graduate Medical Education (ACGME).

Mentorship can be a powerful and life-altering experience during residency training, but there are few articles discussing mentorship models within neurosurgery. In this study, we surveyed US neurosurgical department mentorship practices and linked them to resident outcomes from the Accreditation Council for Graduate Medical Education (ACGME), including resident survey responses, board pass rates, and scholarly activity. A 19-question survey was conducted from October to December 2017 with the assistance of the Society of Neurological Surgeons. De-identified data were then obtained from the ACGME and correlated to these results. Out of 110 programs, 80 (73%) responded to the survey and gave informed consent. The majority (65%) had a formal mentorship program and assigned mentor relationships based on subspecialty or research interest. Barriers to mentorship were identified as time and faculty/resident "buy-in." Mentorship programs established for 5 or more years had superior resident ACGME outcomes, such as board pass rates, survey results, and scholarly activity. There was not a significant difference in ACGME outcomes among programs with formal or informal/no mentorship model (P = .17). Programs that self-identified as having an "unsuccessful" mentorship program had significant increases in overall negative resident evaluations (P = .02). Programs with well-established mentorship programs were found to have superior ACGME resident survey results, board pass rates, and more scholarly activity. There was not a significant difference among outcomes and the different models of formal mentorship practices. Barriers to mentorship, such as time and faculty/resident "buy-in," are identified.
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October 2020

Application of the Preventable Shunt Revision Rate to an Adult Population.

World Neurosurg 2020 Feb 9;134:e815-e821. Epub 2019 Nov 9.

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA; Semmes Murphey Clinic, Memphis, Tennessee, USA; Le Bonheur Children's Hospital, Memphis, Tennessee, USA. Electronic address:

Background: The preventable shunt revision rate (PSRR) was recently introduced in pediatric hydrocephalus as a quality metric for shunt surgery. We evaluated the PSRR in an adult hydrocephalus population.

Methods: All ventricular shunt operations (January 1, 2013 to March 31, 2018) performed at a university-based teaching hospital were included. For any index surgery (de novo or revision) resulting in reoperation within 90 days, the index surgery details were collected, and a consensus decision was reached regarding whether the failure had been potentially avoidable. Preventable failure was defined as failure due to infection, malposition, disconnection, migration, or kinking. The 90-day shunt failure rate and PSRR were calculated. Bivariate analyses were performed to evaluate the individual effects of each independent variable on preventable shunt failure.

Results: A total of 318 shunt operations had been performed in 245 patients. Most patients were women (62%), with a median age of 48.2 years (interquartile range, 31.2-63.2 years). Most had had ventriculoperitoneal shunts placed (86.5%), and just more than one half were new shunts (51.6%). A total of 53 cases (16.7%) in 42 patients experienced shunt failure within 90 days of the index operation. Of these, 27 failures (8.5% of the total cases; 51% of the failures) were considered potentially preventable. The most common reasons were infection (37%; n = 10) and malposition of the proximal and distal catheters (both 25.9%; n = 7). Age was the only statistically significant difference between the 2 groups, with the patients experiencing preventable shunt failure older than those without preventable shunt failure (51.4 vs. 37.1 years; P = 0.017).

Conclusions: The 90-day PSRR can be applied to an adult population and serve as a quality metric.
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February 2020

Evaluation and treatment of children with radiation-induced cerebral vasculopathy.

J Neurosurg Pediatr 2019 Sep 20:1-9. Epub 2019 Sep 20.

Departments of1Neurosurgery and.

Objective: Stenoocclusive cerebral vasculopathy is an infrequent delayed complication of ionizing radiation. It has been well described with photon-based radiation therapy but less so following proton-beam radiotherapy. The authors report their recent institutional experience in evaluating and treating children with radiation-induced cerebral vasculopathy.

Methods: Eligible patients were age 21 years or younger who had a history of cranial radiation and subsequently developed vascular narrowing detected by MR arteriography that was significant enough to warrant cerebral angiography, with or without ischemic symptoms. The study period was January 2011 to March 2019.

Results: Thirty-one patients met the study inclusion criteria. Their median age was 12 years, and 18 (58%) were male. Proton-beam radiation therapy was used in 20 patients (64.5%) and photon-based radiation therapy was used in 11 patients (35.5%). Patients were most commonly referred for workup as a result of incidental findings on surveillance tumor imaging (n = 23; 74.2%). Proton-beam patients had a shorter median time from radiotherapy to catheter angiography (24.1 months [IQR 16.8-35.4 months]) than patients who underwent photon-based radiation therapy (48.2 months [IQR 26.6-61.1 months]; p = 0.04). Eighteen hemispheres were revascularized in 15 patients. One surgical patient suffered a contralateral hemispheric infarct 2 weeks after revascularization; no child treated medically (aspirin) has had a stroke to date. The median follow-up duration was 29.2 months (IQR 21.8-54.0 months) from the date of the first catheter angiogram to last clinic visit.

Conclusions: All children who receive cranial radiation therapy from any source, particularly if the parasellar region was involved and the child was young at the time of treatment, require close surveillance for the development of vasculopathy. A structured and detailed evaluation is necessary to determine optimal treatment.
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http://dx.doi.org/10.3171/2019.7.PEDS19188DOI Listing
September 2019

Management of sterile abdominal pseudocysts related to ventriculoperitoneal shunts.

J Neurosurg Pediatr 2019 Oct 11:1-5. Epub 2019 Oct 11.

1Pediatric Neurosurgery Associates at Children's Healthcare of Atlanta.

Objective: There are many known complications associated with CSF shunts. One of the more rare ones is a sterile abdominal pseudocyst due to decreased peritoneal absorption. This study was undertaken to detail the presentation, evaluation, and management of this unusual shunt-related event.

Methods: Patients presenting with ventriculoperitoneal shunt (VPS)-related sterile abdominal pseudocysts treated at two institutions between 2013 and 2018 were included. Patients who had undergone abdominal surgery or shunt revisions within a 12-month period preceding presentation were excluded. Information was collected regarding clinical characteristics; hospital course, including surgical intervention(s); and any subsequent complications. Special attention was given to the eventual surgery after pseudocyst resolution, including the use of laparoscopy for peritoneal catheter placement, distal shunt conversion (i.e., in the atrium or pleural cavity), endoscopic third ventriculostomy, or shunt removal. The timing and nature of any subsequent shunt failures were also noted.

Results: Twenty-eight patients met the study criteria, with a mean age of 10 years. The most common etiology of hydrocephalus was intraventricular hemorrhage of prematurity. All shunts were externalized at presentation. One shunt was removed without subsequent internalization. Distal catheters were re-internalized back into the peritoneal cavity in 11 patients (laparoscopy was used in 8 cases). Fourteen shunts were converted to a ventriculoatrial shunt (VAS), and two to a ventriculopleural (VPlS). Two VPSs failed due to a recurrent pseudocyst. The total all-cause failure rates at 1 year were as follows: 18% for VPSs and 50% for VASs.

Conclusions: Following treatment of a VPS-related sterile abdominal pseudocyst, laparoscopy-assisted placement of the distal catheter in the peritoneum is a viable and safe option for select patients, compared to a VAS or VPlS.
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October 2019

Shunt Failure-The First 30 Days.

Neurosurgery 2020 07;87(1):123-129

Department of Neurosurgery, The University of Tennessee Health Science Center, Memphis, Tennessee.

Background: Incontrovertible predictors of shunt malfunction remain elusive.

Objective: To determine predictors of shunt failure within 30 d of index surgery.

Methods: This was a single-center retrospective cohort study from January 2010 through November 2016. Using a ventricular shunt surgery research database, clinical and procedural variables were procured. An "index surgery" was defined as implantation of a new shunt or revision or augmentation of an existing shunt system. The primary outcome was shunt failure of any kind within the first 30 days of index surgery. Bivariate models were created, followed by a final multivariable logistic regression model using a backward-forward selection procedure.

Results: Our dataset contained 655 unique patients with a total of 1206 operations. The median age for the cohort at the time of first shunt surgery was 4.6 yr (range, 0-28; first and third quartile, .37 and 11.8, respectively). The 30-day failure rates were 12.4% when analyzing the first-index operation only (81/655), and 15.7% when analyzing all-index operations (189/1206). Small or slit ventricles at the time of index surgery and prior ventricular shunt operations were found to be significant covariates in both the "first-index" (P < .01 and P = .05, respectively) and "all-index" (P = .02 and P < .01, respectively) multivariable models. Intraventricular hemorrhage at the time of index surgery was an additional predictor in the all-index model (P = .01).

Conclusion: This study demonstrates that only 3 variables are predictive of 30-day shunt failure when following established variable selection procedures, 2 of which are potentially under direct control of the surgeon.
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July 2020

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Closure of Myelomeningocele Within 48 Hours to Decrease Infection Risk.

Neurosurgery 2019 09;85(3):E412-E413

Goryeb Children's Hospital, Morristown, NJ; Rutgers Department of Neurological Surgery, Newark, New Jersey.

Background: Appropriate timing for closure of myelomeningocele (MM) varies in the literature. Older studies present 48 h as the timeframe after which infection complication rates rise.

Objective: The objective of this guideline is to determine if closing the MM within 48 h decreases the risk of wound infection or ventriculitis.

Methods: The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full text articles were then reviewed and when appropriate, included in the evidentiary table. The class of evidence was evaluated, discussed, and assigned to each study that met inclusion criteria.

Results: A total of 148 abstracts were identified and reviewed. A total of 31 articles were selected for full text analysis. Only 4 of these studies met inclusion criteria.

Conclusion: There is insufficient evidence that operating within 48 h decreases risk of wound infection or ventriculitis in 1 Class III study. There is 1 Class III study that provides evidence of global increase in postoperative infection after 48 h, but is not specific to wound infection or ventriculitis. There is 1 Class III study that provides evidence if surgery is going to be delayed greater than 48 h, antibiotics should be given.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-4.
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September 2019

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Management of Patients With Myelomeningocele: Whether Prenatal or Postnatal Closure Affects Future Ambulatory Status.

Neurosurgery 2019 09;85(3):E409-E411

Goryeb Children's Hospital, Morristown, New Jersey; Rutgers Department of Neurological Surgery, Newark, New Jersey.

Background: Myelomeningocele (MM) is an open neural tube defect treated by pediatric neurosurgeons with prenatal or postnatal closure.

Objective: The objective of this systematic review was to answer the question: What is the evidence for the effectiveness of prenatal vs postnatal closure of MM regarding short and long-term ambulatory status? Treatment recommendations were provided based on the available evidence.

Methods: The National Library of Medicine PubMed database and Embase were queried using MeSH headings and keywords relevant to ambulatory status after prenatal or postnatal closure of MM. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidence table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III).

Results: One randomized controlled trial (Class II) and 3 retrospective cohort studies (Class III) were included as evidence. Initial ambulatory status depended on anatomic level of the neural tube defect. In the short term, prenatal closure may improve ambulatory status compared to postnatal closure. Spinal cord tethering or dermoid inclusion cyst has been associated with neurologic deterioration in infants closed in utero and after birth. Ambulation may cease in both groups over time. No long-term studies evaluated whether there is a difference in the ability to ambulate upon reaching adulthood.

Conclusion: Prenatal closure of MM may improve ambulatory status in the short term (Level II). Spinal cord tethering in both groups caused deterioration in the ability to walk. Evaluation and treatment of spinal cord tethering may help maintain ambulatory status (Level III). No studies evaluate whether prenatal or postnatal repair provides improved ability to ambulate upon reaching adulthood.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-3.
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September 2019

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Shunt-Dependent Hydrocephalus in Infants With Myelomeningocele After Prenatal Versus Postnatal Repair.

Neurosurgery 2019 09;85(3):E405-E408

Goryeb Children's Hospital, Morristown, NJ; Rutgers Department of Neurological Surgery, Newark, New Jersey.

Background: Myelomeningocele (MM) is a condition that is responsible for considerable morbidity in the pediatric population. A significant proportion of the morbidity related to MM is attributable to hydrocephalus and the surgical management thereof. Postnatal repair remains the most common form of treatment; however, increased rates of prenatal diagnosis, advances in fetal surgery, and a hypothesis that neural injury continues in utero until the MM defect is repaired have led to the development and evaluation of prenatal surgery as a means to improve outcomes in afflicted infants.

Objective: The objective of this guideline is to systematically evaluate the literature to determine whether there is a difference in the proportion of patients who develop shunt-dependent hydrocephalus in infants who underwent prenatal MM repair compared to infants who had postnatal repair.

Methods: The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full-text articles were then reviewed, and when appropriate, included as evidence.

Results: A total of 87 abstracts were identified and reviewed by 3 independent reviewers. Thirty-nine full-text articles were selected for analysis. Three studies met selection criteria and were included in the evidence table.

Conclusion: Class I evidence from 1 study and class III evidence from 2 studies suggest that, in comparison to postnatal repair, prenatal surgery for MM reduces the risk of developing shunt-dependent hydrocephalus. Therefore, prenatal repair of MM is recommended for those fetuses who meet specific criteria for prenatal surgery to reduce the risk of developing shunt-dependent hydrocephalus (level I). Differences between prenatal and postnatal repair with respect to the requirement for permanent cerebrospinal fluid diversion should be considered alongside other relevant maternal and fetal factors when deciding upon a preferred method of MM closure. The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-2.
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September 2019

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Pediatric Myelomeningocele: Executive Summary.

Neurosurgery 2019 09;85(3):299-301

Department of Neurosurgery, Mercer University Medical School, Macon, Georgia.

Background: The incidence of spina bifida (SB) in the developing world is higher than in the United States because of malnutrition and folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible.

Objective: The objective of the guidelines are, (1) To create clinical recommendations for best practices, based on a systematic review and analysis of available literature, (2) to obtain multi-disciplinary endorsement of these guidelines from relevant organizations, and (3) to disseminate the educational content to physicians to improve the care of infants with MM.

Methods: The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review.

Results: Guidelines authors aimed to systematically review the literature and make evidence based recommendations about the timing of closure after birth, hydrocephalus, the impact of prenatal closure, and the effect of prenatal closure on ambulation ability and tethered spinal cord. Evidence concerning persistent ventriculomegaly and cognitive impairment was also evaluated. Hundreds of abstracts were identified and reviewed for each of the 5 topics. A total of 14 studies met stringent inclusion criteria.

Conclusion: Based on a comprehensive systematic review, a total of 5 clinical practice recommendations were developed, with 1 Level I, 2 Level II and 2 Level III recommendations.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-1.
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September 2019