Analysis of gliomas DNA methylation: Assessment of pre-analytical variables.

Precision oncology is driven by molecular biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase ( MGMT ) gene DNA promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage before fixing, sampling, and processing are major sources of errors and batch effects, that are further confounded by intra-tumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL) and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter CpG methylation was examined in 173 surgical samples from 90 individuals, 50 of these were used for intra-tumor heterogeneity studies. MGMT promoter methylation levels in paired frozen and formalin fixed paraffin embedded (FFPE) samples were very close, confirming suitability of FFPE for MGMT promoter methylation analysis in clinical settings. Matrix MeDIP-qPCR yielded similar results to methylation specific PCR (MS-PCR). Warm ex-vivo ischemia (37°C up to 4hrs) and 3 cycles of repeated sample thawing and freezing did not alter 5mC levels at MGMT promoter, exon and upstream enhancer regions, demonstrating the resistance of DNA methylation to the most common variations in sample processing conditions that might be encountered in research and clinical settings. 20-30% of specimens exhibited intratumor heterogeneity in the MGMT DNA promoter methylation. Collectively these data demonstrate that variations in sample fixation, ischemia duration and temperature, and DNA methylation assay technique do not have significant impact on assessment of MGMT promoter methylation status. However, intratumor methylation heterogeneity underscores the need for histologic verification and value of multiple biopsies at different GBM geographic tumor sites in assessment of MGMT promoter methylation. Matrix-MeDIP-seq analysis revealed that MGMT promoter methylation status clustered with other differentially methylated genomic loci (e.g. HOXA and lncRNAs), that are likewise resilient to variation in above post-resection pre-analytical conditions. These MGMT -associated global DNA methylation patterns offer new opportunities to validate more granular data-based epigenetic GBM clinical biomarkers where the CryoGrid-PIXUL-Matrix toolbox could prove to be useful.

Looking beyond year 1 in the molecular era of pediatric brain tumor diagnosis: confirmatory testing of germline variants found on tumor sequencing.

Purpose: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. Patients and Methods: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest. Results: Molecular sequencing of 88 patients' tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing. Conclusion: Clinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

Intraoperative neuromonitoring potentials and evidence of preserved neuronal circuitry below the anatomical and functional level in patients with complex spinal dysraphism undergoing detethering reoperations.

OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.

Somatic Versus Germline: A Case Series of Three Children With ATM-Mutated Medulloblastoma.

Somatic versus Germline-A Case Series of Three Children with ATM- mutated Medulloblastoma.

Perioperative complications and secondary retethering after pediatric tethered cord release surgery.

OBJECTIVE: Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord, which can be secondary to various etiologies. Surgical management of simple tethered cord etiologies (e.g., fatty filum) typically consists of a single-level lumbar laminectomy, intradural exploration, and coagulation and sectioning of the filum. More complex etiologies such as lipomyelomeningoceles or scar formation after myelomeningocele repair involve complex dissection and dural reconstruction. The purpose of this study was to evaluate operative complications and long-term outcomes of secondary retethering related to pediatric tethered cord release (TCR) at a tertiary children's hospital. METHODS: Medical records of children who underwent surgery for TCR from July 2014 to March 2023 were retrospectively reviewed. Data collected included demographics, perioperative characteristics, surgical technique, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat TCR surgery. Univariate and multivariate analyses were performed to identify risk factors associated with complications and secondary retethering. RESULTS: A total of 363 TCR surgeries (146 simple, 217 complex) in 340 patients were identified. The mean follow-up was 442.8 ± 662.2 days for simple TCRs and 733.9 ± 750.3 days for complex TCRs. The adjusted 60-day complication-free survival rate was 96.3% (95% CI 91.3%-98.4%) for simple TCRs and 88.7% (95% CI 82.3%-91.4%) for complex TCRs. Lower weight, shorter surgical times, and intensive care unit admission were associated with complications for simple TCRs. Soft-tissue drains increased complications for complex TCRs. The secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival rates in complex cases were 94.7% (95% CI 89.1%-97.4%), 77.7% (95% CI 67.3%-85.3%), and 62.6% (95% CI 46.5%-75.1%), respectively. Multivariate analysis revealed that prior detethering (OR 8.15, 95% CI 2.33-28.50; p = 0.001) and use of the operative laser (OR 10.43, 95% CI 1.36-80.26; p = 0.024) were independently associated with secondary retethering in complex cases. CONCLUSIONS: This is the largest series to date examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks of complications and secondary retethering. Modifiable risk factors such as operative laser use influenced secondary retethering in complex cases.

Pediatric Cranial Vault and Skull Base Fractures.

Cranial vault and skull base fractures in children are distinctly different from those seen in adults. Pediatric skull fractures have the benefit of greater capacity to remodel; however, the developing pediatric brain and craniofacial skeleton present unique challenges to diagnosis, natural history, and management. This article discusses the role of surgical treatment of these fractures, its indications, and techniques.

Two Year Comparison of Sagittal Synostosis Morphometric Outcomes Following Open Posterior Expansion Versus Endoscopic Strip Craniectomy with Helmet Molding Performed before Four Months of Age.

BACKGROUND: Open middle and posterior cranial vault expansion (OPVE) or endoscopic (ES) strip craniectomy are two surgical techniques for normalization of head shape in isolated sagittal synostosis. This study aims to compare two-year cranial morphometrics after these two approaches. METHODS: We performed morphometric analysis on preoperative (t0), immediately post-operative (t1) and 2-year (t2) postoperative CT scans of patients who underwent OPVE or ES prior to 4 months of age. Perioperative data and morphometrics were compared between the two groups and age-matched controls. RESULTS: Nineteen patients were included in the ES cohort, 19 age-matched patients in the OPVE cohort, and 57 as controls. Median surgery time and blood transfusion volume were less for the ES approach (118 min; 0cc) compared to OPVE (204 min; 250cc). Anthropometric measurements after OPVE were closer normal controls at t1 compared to ES, but the skull shapes were comparable at t2. In the mid-sagittal plane, anterior vault was higher after OPVE at t2 compared to both ES and controls, but the posterior length was shorter and closer to controls than the ES cohort. Cranial volumes were like controls for both cohorts at t2. There was no difference in complication rate. CONCLUSIONS: Both OPVE and ES techniques result in normalization of cranial shape in patients with isolated sagittal synostosis after two years with minimal morphometric differences. Family decision-making between the two approaches should be based on age at presentation, avoidance of blood transfusion, scar pattern, and availability of helmet molding and not on expected outcome. LEVEL OF EVIDENCE: III.

A Comparison of Clinical Outcomes for Subependymal Giant Cell Astrocytomas Treated with Laser Interstitial Thermal Therapy, Open Surgical Resection, and mTOR Inhibitors.

INTRODUCTION: Subependymal giant cell astrocytoma (SEGA) is the most common CNS tumor in patients with tuberous sclerosis complex (TSC). Although these are benign, their proximity to the foramen of Monroe frequently causes obstructive hydrocephalus, a potentially fatal complication. Open surgical resection has been the mainstay of treatment; however, this can cause significant morbidity. The development of mTOR inhibitors has changed the treatment landscape, but there are limitations to their use. Laser interstitial thermal therapy (LITT) is an emerging treatment modality that has shown promise in treatment of a variety of intracranial lesions, including SEGAs. We present a single institution, retrospective study of patients treated for SEGAs with LITT, open resection, mTOR inhibitors, or a combination of these modalities. The primary study outcome was tumor volume at most recent follow-up compared with volume at treatment initiation. The secondary outcome was clinical complications associated with treatment modality. METHODS: Retrospective chart review was performed to identify patients with SEGAs treated at our institution from 2010 to 2021. Demographics, treatment information, and complications were collected from the medical record. Tumor volumes were calculated from imaging obtained at initiation of treatment and at most recent follow-up. Kruskal-Wallis nonparametric testing was used to assess differences in tumor volume and follow-up duration between groups. RESULTS: Four patients underwent LITT (3 with LITT only), three underwent open surgical resection, and four were treated with mTOR inhibitors only. Mean percent tumor volume reduction for each group was 48.6 ± 13.8, 90.7 ± 39.8, and 67.1 ± 17.2%, respectively. No statistically significant difference was identified comparing percent tumor volume reduction between the three groups (p = 0.0513). Additionally, there was no statistically significant difference in follow-up duration between groups (p = 0.223). Only 1 patient in our series required permanent CSF diversion and 4 discontinued or decreased the dose of mTOR inhibitor due to either cost or side effects. CONCLUSIONS: Our study suggests that LITT could be considered as a treatment option for SEGAs as it was effective in reducing tumor volume with very few complications. This modality is less invasive than open resection and may be an alternative for patients who are not candidates for mTOR inhibitors. We recommend an updated paradigm for SEGA treatment which includes LITT in select cases after consideration of patient-specific factors.

Remote patient monitoring following full endoscopic spine surgery: feasibility and patient satisfaction.

OBJECTIVE: The utilization of telemedicine in healthcare has increased dramatically during the recent COVID-19 pandemic. This study aimed to investigate the feasibility to perform remote patient monitoring after full endoscopic spine surgery via a smartphone application that also allows communication with patients. METHODS: A smartphone application (SPINEhealthie) was designed at the University of Washington and used to collect patient-reported outcome measures (PROMs) and to provide chat communication between patients and their care team. A total of 71 patients were included in the study and prospectively followed for 3 months postoperatively. Patient demographic characteristics, compliance with surveys, and frequency of chat utilization were recorded. The ease of use, the participants' experiences with the app interface design, and the usefulness of the app were assessed by using the mHealth App Usability Questionnaire (MAUQ). RESULTS: Of all eligible patients, 71/78 (91.0%) agreed to participate. Of these, 60 (85%) patients provided at least 1 postoperative PROM. There was good coverage of the immediate postoperative period with 45 (63.4%) patients providing ≥ 5 PROMs within the 1st week after surgery. The authors observed a 33.2% increase in patient compliance in postoperative PROMs and a 45.7% increase in chat function utilization between the first and last of the three enrollment periods of the study, during which continuous updates were made to improve the app's functionality. Sixty-two (87.3%) patients responded to the user satisfaction survey after using the app for at least 40 days. The MAUQ results revealed excellent rates of satisfaction for ease of use (78.6% of the maximum score), app interface design (71.4%), and usefulness (71.4%), resulting in a total mean MAUQ score of 110 (74.8%). Communication with the doctor (38 votes) was found to be the top feature of the app. Additionally, physical therapy instructions (33 votes) and imaging review (29 votes) were the top two features that patients would like to see in future app versions. Lastly, the authors have presented a case example of a 68-year-old man who used the app for postoperative monitoring and communication after undergoing a two-level lumbar endoscopic unilateral laminotomy for bilateral decompression. CONCLUSIONS: Postoperative remote patient monitoring and communication after full endoscopic surgery is feasible using the SPINEhealthie app. Importantly, patients were willing to share their medical information using a mobile device, and they were eager to use it postoperatively as a supplementary tool.

Morphometric Outcomes of Nonsyndromic Sagittal Synostosis following Open Middle and Posterior Cranial Vault Expansion.

BACKGROUND: This study aimed to quantify the change in three-dimensional skull morphometrics for patients with sagittal synostosis at presentation, after surgery, and at 2-year follow-up. METHODS: Computed tomography scans from 91 patients with isolated SS were age-, sex-, and race-matched with those from 273 controls. The authors performed vector analysis with linear regressions to model the effect of open middle and posterior cranial vault remodeling on cranial shape and growth. RESULTS: Anterior cranial volume, bossing angle, and frontal shape were not changed by surgery but normalized without surgical intervention by 2 years. Biparietal narrowing and middle cranial volume were corrected after surgery and maintained at 2 years. Occipital protuberance was improved after surgery and normalized at 2 years. Posterior cranial volume was decreased by occipital remodeling and remained slightly lower than control volumes at 2 years, whereas middle vault volume was larger than in controls. Residual deformities that persisted at 2 years were decreased superolateral width at the level of opisthion and increased anterosuperior height (vertex bulge). Linear models suggested older age at surgery resulted in more scaphocephaly and enlarged posterior cranial vault volumes at 2 years but did not affect other volume outcomes. Preoperative severity was the variable most predictive of 2-year morphometrics. CONCLUSIONS: Initial severity of sagittal synostosis deformity was the best predictor of 2-year morphometric outcomes. Upper posterior cranial width decreases with time after surgery and an anterior vertex bulge can persist after open surgery, but frontal dysmorphology self-corrects without surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Cranial Shape Changes in Nonsyndromic Unilateral Lambdoid Synostosis after Open Posterior Vault Remodeling.

BACKGROUND: The purpose of this study was to quantify change in cranial morphology in patients with nonsyndromic unilateral lambdoid craniosynostosis (ULC) from presentation (t0), after open posterior switch-cranioplasty (t1), and at 2-year follow-up (t2). METHODS: Volumetric, linear, and angular analysis were performed on computed tomographic scans at the three time points and against normal control subjects. Significance was set at P < 0.05. RESULTS: Twenty-two patients were included. ULC cranial vault asymmetry index was higher than in control subjects before surgery (6.22 ± 3.55) but decreased after surgery (3.00 ± 2.53) to become comparable with the normal asymmetry range present in the controls. After surgery, both diagonals increased, but more on the fused side. In the 2 years after surgery, both diagonals in patients with ULC grew proportionately, but the fused diagonal remained slightly shorter than the patent side. Total cranial volume was higher in patients with ULC than in control subjects after surgery but became comparable at t2. Cranial base angulation improved by t2 but did not approach normal, and ear position remained unchanged. The facial twist was higher than in controls at t0 and t1 but was comparable at t2. Coronal asymmetry improved with surgery but remained undercorrected at t2, with the greatest residual asymmetry at opisthion. CONCLUSIONS: Open-switch cranioplasty normalizes cranial vault asymmetry index by increasing the fused cranial diagonal more than the patent side and is stable at 2 years. Skull base twist does not normalize, but facial twist approaches normal. Technique improvement should focus on residual coronal asymmetry present at opisthion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Severe Polyethylene Glycol Allergy Considerations for Perioperative Management: A Case Report.

Patients with severe polyethylene glycol (PEG) allergies face broad challenges, especially when presenting to the hospital for surgery, as PEG is used often as an excipient in medications and in medical supplies. Although rare, this allergy is increasingly reported and likely underdiagnosed. We present a patient with known past anaphylactic reaction to PEG and a detailed account of her perioperative course. More broadly, we provide recommendations and resources for the safe management of similar patients with a severe PEG allergy.

Progressive-Tension Sutures in Reconstruction of Posterior Trunk Defects in Pediatric Patients: A Prospective Series.

SUMMARY: Following neurosurgical repair of spinal dysraphism defects, soft-tissue reconstruction is often required to obtain robust coverage of the dura. Layered closure utilizing local muscle and muscle fascia has proven reliable for this purpose, but it often results in significant dead space necessitating closed suction drainage. Progressive-tension sutures have been reported as an alternative to drains for prevention of fluid collection in several other procedures. In this study, the use of progressive-tension sutures for eliminating subcutaneous dead space and obtaining tension-free skin closure was prospectively evaluated in pediatric patients undergoing soft-tissue reconstruction for congenital spinal anomalies. Primary outcomes of interest included wound breakdown, seroma, hematoma, and cerebrospinal fluid leak. Patients were excluded if a lumbar, submuscular, or subcutaneous drain was placed during the index procedure. Over a 3-year period, 45 patients underwent muscle flap reconstruction for coverage of dural defects. The primary diagnoses were myelomeningocele (10 patients), lipomyelomeningocele (eight patients), myelocystocele (three patients), tethered cord release (15 patients), meningocele (three patients), spinal tumor (two patients), and hardware exposure following spinal instrumentation (three patients). During the follow-up period, three patients (6.7 percent) had postoperative wound complications. One patient had superficial dehiscence, one had cerebrospinal fluid leak requiring operative revision, and one had a surgical site infection necessitating operative drainage. No patients developed hematomas, seromas, cerebrospinal fluid fistulae, or wound breakdown requiring operative revision. The use of progressive-tension sutures is an effective method for eliminating subcutaneous dead space in pediatric soft-tissue reconstruction and eliminates the need for drain placement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Morphologic Differences in Sagittal Synostosis with Age before Surgery.

BACKGROUND: It is important to determine whether sagittal synostosis-associated scaphocephaly is static in the presurgical period, or whether there are morphologic differences with time to include in surgical decision-making. The authors' purpose was to perform cross-sectional analysis of cranial morphology before any surgical intervention in children with sagittal synostosis younger than 9 months compared to matched controls. METHODS: The authors performed morphometric analysis on computed tomographic scans from 111 untreated isolated sagittal synostosis patients younger than 9 months and 37 age-matched normal controls. The authors divided the patients into three age groups and performed statistical comparison between sagittal synostosis and controls for each group. RESULTS: Sagittal synostosis cephalic indices were stable and lower in patients than in controls across groups. Total cranial volume was equivalent, but sagittal synostosis patients had a greater posterior volume than controls at all ages and a smaller middle fossa volume at older ages. Pterional width was greater in sagittal synostosis patients than in controls for each age group. Frontal bossing vectors were most severe in the youngest age groups and least in the older group. Occipital protuberance was consistent across the age groups. CONCLUSIONS: Upper parietal narrowing and occipital protuberance were the consistent deformities across age groups, with the most parietal constriction seen in older patients. Frontal bossing was not consistent and was more severe in the younger patients. The authors did not detect significant pterional constriction, and the appearance of constriction is relative to adjacent morphology and not absolute. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Two cases of pineal anlage tumor with molecular analysis.

Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.

Socioeconomic and demographic factors in the diagnosis and treatment of Chiari malformation type I and syringomyelia.

OBJECTIVE: The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS: The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS: A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS: Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

Concurrent decompression and resection versus decompression with delayed resection of acutely ruptured brain arteriovenous malformations.

OBJECTIVE: Brain arteriovenous malformations (bAVMs) most commonly present with rupture and intraparenchymal hemorrhage. In rare cases, the hemorrhage is large enough to cause clinical herniation or intractable intracranial hypertension. Patients in these cases require emergent surgical decompression as a life-saving measure. The surgeon must decide whether to perform concurrent or delayed resection of the bAVM. Theoretical benefits to concurrent resection include a favorable operative corridor created by the hematoma, avoiding a second surgery, and more rapid recovery and rehabilitation. The objective of this study was to compare the clinical and surgical outcomes of patients who had undergone concurrent emergent decompression and bAVM resection with those of patients who had undergone delayed bAVM resection. METHODS: The authors conducted a 15-year retrospective review of consecutive patients who had undergone microsurgical resection of a ruptured bAVM at their institution. Patients presenting in clinical herniation or with intractable intracranial hypertension were included and grouped according to the timing of bAVM resection: concurrent with decompression (hyperacute group) or separate resection surgery after decompression (delayed group). Demographic and clinical characteristics were recorded. Groups were compared in terms of the primary outcomes of hospital and intensive care unit (ICU) lengths of stay (LOSs). Secondary outcomes included complete obliteration (CO), Glasgow Coma Scale score, and modified Rankin Scale score at discharge and at the most recent follow-up. RESULTS: A total of 35/269 reviewed patients met study inclusion criteria; 18 underwent concurrent decompression and resection (hyperacute group) and 17 patients underwent emergent decompression only with later resection of the bAVM (delayed group). Hyperacute and delayed groups differed only in the proportion that underwent preresection endovascular embolization (16.7% vs 76.5%, respectively; p < 0.05). There was no significant difference between the hyperacute and delayed groups in hospital LOS (26.1 vs 33.2 days, respectively; p = 0.93) or ICU LOS (10.6 vs 16.1 days, respectively; p = 0.69). Rates of CO were also comparable (78% vs 88%, respectively; p > 0.99). Medical complications were similar in the two groups (33% hyperacute vs 41% delayed, p > 0.99). Short-term clinical outcomes were better for the delayed group based on mRS score at discharge (4.2 vs 3.2, p < 0.05); however, long-term outcomes were similar between the groups. CONCLUSIONS: Ruptured bAVM rarely presents in clinical herniation requiring surgical decompression and hematoma evacuation. Concurrent surgical decompression and resection of a ruptured bAVM can be performed on low-grade lesions without compromising LOS or long-term functional outcome; however, the surgeon may encounter a more challenging surgical environment.

Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma-and individual participant data meta-analysis (IPDMA).

PURPOSE: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature. METHODS: A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression. RESULTS: We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression. CONCLUSION: Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.

Pediatric hemispherectomy outcome: Adaptive functioning, intelligence, and memory.

OBJECTIVE: Our purpose was to characterize neuropsychological evaluation (NP) outcome following functional hemispherectomy in a large, representative cohort of pediatric patients. METHODS: We evaluated seizure and NP outcomes and medical variables for all post-hemispherectomy patients from Seattle Children's Hospital epilepsy surgery program between 1996 and 2020. Neuropsychological evaluation outcome tests used were not available on all patients due to the diversity of patient ages and competency that is typical of a representative pediatric cohort; all patients had at least an adaptive functioning or intelligence measure, and a subgroup had memory testing. RESULTS: A total of 71 hemispherectomy patients (37 right; 34 females) yielded 66 with both preoperative (PREOP) plus postoperative (POSTOP) NPs and 5 with POSTOP only. Median surgery age was 5.7 (IQR 2-9.9) years. Engel classification indicated excellent seizure outcomes: 59 (84%) Class I, 6 (8%) Class II, 5 (7%) Class III, and 1 (1%) Class IV. Medical variables - including seizure etiology, surgery age, side, presurgical seizure duration, unilateral or bilateral structural abnormalities, secondarily generalized motor seizures - were not associated with either Engel class or POSTOP NP scores, though considerable heterogeneity was evident. Median PREOP and POSTOP adaptive functioning (PREOP n = 45, POSTOP n = 48) and intelligence (PREOP n = 29, POSTOP n = 36) summary scores were exceptionally low and did not reveal group decline from PREOP to POSTOP. Fifty-five of 66 (85%) cases showed stability or improvement. Specifically, 5 (8%) improved; 50 (76%) showed stability; and 11 (16%) declined. Improve and decline groups showed clinically interesting, but not statistical, differences in seizure control and age. Median memory summary scores were low and also showed considerable heterogeneity. Overall median PREOP to POSTOP memory scores (PREOP n = 16, POSTOP n = 24) did not reveal declines, and verbal memory scores improved. Twenty six percent of intelligence and 33% of memory tests had verbal versus visual-spatial discrepancies; all but one favored verbal, regardless of hemispherectomy side. SIGNIFICANCE: This large, single institution study revealed excellent seizure outcome in 91% of all 71 patients plus stability and/or improvement of intelligence and adaptive functioning in 85% of 66 patients who had PREOP plus POSTOP NPs. Memory was similarly stable overall, and verbal memory improved. Medical variables did not predict group NP outcomes though heterogeneity argues for further research. This study is unique for cohort size, intelligence plus memory testing, and evidence of primacy of verbal over visual-spatial development, despite hemispherectomy side. This study reinforces the role of hemispherectomy in achieving good seizure outcome while preserving functioning.