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Study Design: Systematic review., Objective: To identify commonly reported indications and outcomes in spinal column shortening (SCS) procedures., Background: SCS is a surgical procedure used in patients with tethered cord syndrome-characterized by abnormal attachment of neural components to surrounding tissues-to shorten the vertebral column, release tension on the spinal cord/neural elements, and alleviate associated symptoms., Patients and Methods: PubMed and EMBASE searches captured SCS literature published between 1950 and 2023. Prospective/retrospective cohort studies and case series were included without age limit or required follow-up period. Review articles without new patient presentations, meta-analyses, systematic reviews, conference abstracts, and letters were excluded. Studies included adult and pediatric patients., Results: The 29 identified studies represented 278 patients (aged 5-76 yr). In 24.1% of studies, patients underwent primary tethered cord syndrome intervention through SCS. In 41.4% of studies, patients underwent SCS after failed previous primary detethering (24.1% of studies were mixed and 10.3% were unspecified). The most commonly reported nongenitourinary/bowel surgical indications were back pain (55.2%), lower-extremity pain (48.3%), lower-extremity weakness (48.3%), lower-extremity numbness (34.5%), and lower-extremity motor dysfunction (34.5%). Genitourinary/bowel symptoms were most often described as nonspecific bladder dysfunction (58.6%), bladder incontinence (34.5%), and bowel dysfunction (31.0%). After SCS, nongenitourinary/bowel outcomes included lower-extremity pain (44.8%), back pain (31.0%), and lower-extremity sensory and motor function (both 31.0%). Bladder dysfunction (79.3%), bowel dysfunction (34.5%), and bladder incontinence (13.8%) were commonly reported genitourinary/bowel outcomes. In total, 40 presenting surgical indication categories and 33 unique outcome measures were reported across studies. Seventeen of the 278 patients (6.1%) experienced a complication., Conclusion: The SCS surgical literature displays variability in operative indications and postoperative outcomes. The lack of common reporting mechanisms impedes higher-level analysis. A standardized outcomes measurement tool, encompassing both patient-reported outcome measures and objective metrics, is necessary., Level of Evidence: Level IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM., Competing Interests: Declaration of interests The authors declare no competing interests.

Objective: Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers., Methods: Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed., Results: Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals., Conclusions: In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

Purpose: There is limited information on the clustering or co-occurrence of complications after spinal fusion surgery for neuromuscular disease in children. We aimed to identify the frequency and predictive factors of co-occurring perioperative complications in these children., Methods: In this retrospective database cohort study, we identified children (ages 10-18 years) with neuromuscular scoliosis who underwent elective spinal fusion in 2012-2020 from the National Surgical Quality Improvement Program-Pediatric database. The rates of co-occurring complications within 30 days were calculated, and associated factors were identified by logistic regression analysis. Correlation between a number of complications and outcomes was assessed., Results: Approximately 11% (709/6677 children with neuromuscular scoliosis undergoing spinal fusion had co-occurring complications: 7% experienced two complications and 4% experienced ≥ 3. The most common complication was bleeding/transfusion (80%), which most frequently co-occurred with pneumonia (24%) and reintubation (18%). Surgical time ≥ 400 min (odds ratio (OR) 1.49 [95% confidence interval (CI) 1.25-1.75]), fusion ≥ 13 levels (1.42 [1.13-1.79]), and pelvic fixation (OR 1.21 [1.01, 1.44]) were identified as procedural factors that independently predicted concurrent complications. Clinical risk factors for co-occurring complications included an American Society of Anesthesiologist physical status classification ≥ 3 (1.73 [1.27-2.37]), structural pulmonary/airway abnormalities (1.24 [1.01-1.52]), impaired cognitive status (1.80 [1.41-2.30]), seizure disorder (1.36 [1.12-1.67]), hematologic disorder (1.40 [1.03-1.91], preoperative nutritional support (1.34 [1.08-1.72]), and congenital malformations (1.20 [1.01-1.44]). Preoperative tracheostomy was protective against concurrent complications (0.62 [0.43-0.89]). Significant correlations were found between number of complications and length of stay, non-home discharge, readmissions, and death., Conclusion: Longer surgical time (≥ 400 min), fusion ≥ 13 levels and pelvic fixation are surgical risk factors independently associated with co-occurring complications, which were associated with poorer patient outcomes. Recognizing identified nonmodifiable risk factors might also be important for preoperative planning and risk stratification of children with neuromuscular scoliosis requiring spinal fusion., Level of Evidence: Level IV evidence., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Understanding the complication profile of craniosynostosis surgery is important, yet little is known about complication co-occurrence in syndromic children after multi-suture craniosynostosis surgery. We examined concurrent perioperative complications and predictive factors in this population., Methods: In this retrospective cohort study, children with syndromic diagnoses and multi-suture involvement who underwent craniosynostosis surgery in 2012-2020 were identified from the National Surgical Quality Improvement Program-Pediatric database. The primary outcome was concurrent complications; factors associated with concurrent complications were identified. Correlations between complications and patient outcomes were assessed., Results: Among 5,848 children identified, 161 children (2.75%) had concurrent complications: 129 (2.21%) experienced two complications and 32 (0.55%) experienced ≥ 3. The most frequent complication was bleeding/transfusion (69.53%). The most common concurrent complications were transfusion/superficial infection (27.95%) and transfusion/deep incisional infection (13.04%) or transfusion/sepsis (13.04%). Two cardiac factors (major cardiac risk factors (odds ratio (OR) 3.50 [1.92-6.38]) and previous cardiac surgery (OR 4.87 [2.36-10.04])), two pulmonary factors (preoperative ventilator dependence (OR 3.27 [1.16-9.21]) and structural pulmonary/airway abnormalities (OR 2.89 [2.05-4.08])), and preoperative nutritional support (OR 4.05 [2.34-7.01]) were independently associated with concurrent complications. Children who received blood transfusion had higher odds of deep surgical site infection (OR 4.62 [1.08-19.73]; p = 0.04)., Conclusions: Our results indicate that several cardiac and pulmonary risk factors, along with preoperative nutritional support, were independently associated with concurrent complications but procedural factors were not. This information can help inform presurgical counseling and preoperative risk stratification in this population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST., Methods: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated., Results: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications., Conclusions: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes., Competing Interests: Declaration of interests M.B.-J. is a co-inventor of patent application WO/2018/160496, related to the differentiation of pluripotent stem cells into microglia and co-founder of NovoGlia, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy., Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively., Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (&gt;1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy., Conclusion: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted., (© 2023 S. Karger AG, Basel.)

Background: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS)., Material and Methods: We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3., Results: We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19 months (range: 12-51 months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9 years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS., Conclusions: Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Existing automated seizure detection algorithms report sensitivities between 43% and 77% and specificities between 56% and 90%. The algorithms suffer from false alarms when applied to neonatal EEG because of the high degree of nurse handling and rhythmic patting used to soothe neonates. Computer vision technology that quantifies movement in real time could distinguish artifactual motion and improve automated neonatal seizure detection algorithms., Methods: The authors used video EEG recordings from 43 neonates undergoing monitoring for seizures as part of the NEOLEV2 clinical trial. The Persyst neonatal automated seizure detection algorithm ran in real time during study EEG acquisitions. Computer vision algorithms were applied to extract detailed accounts of artifactual movement of the neonate or people near the neonate though dense optical flow estimation., Results: Using the methods mentioned above, 197 periods of patting activity were identified and quantified, of which 45 generated false-positive automated seizure detection events. A binary patting detection algorithm was trained with a subset of 470 event videos. This supervised detection algorithm was applied to a testing subset of 187 event videos with 8 false-positive events, which resulted in a 24% reduction in false-positive automated seizure detections and a 50% reduction in false-positive events caused by neonatal care patting, while maintaining 11 of 12 true-positive seizure detection events., Conclusions: This work presents a novel approach to improving automated seizure detection algorithms used during neonatal video EEG monitoring. This artifact detection mechanism can improve the ability of a seizure detector algorithm to distinguish between artifact and true seizure activity., Competing Interests: S. Wilson, N. Nierenberg, and M. Scheuer are employees of the company (Persyst) that produces the automated EEG computer software that is used alongside our software algorithm. The other authors have no conflicts of interests to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Background: Ventriculoperitoneal shunt (VPS) placement into the reoperative abdomen can be challenging due to intraperitoneal adhesions. Laparoscopic guidance may provide safe abdominal access and identify an area for optimal cerebrospinal fluid drainage. The study aim was to compare laparoscopic-assisted VPS placement to an "open" approach in patients with prior abdominal surgery., Materials and Methods: A retrospective review was performed of children undergoing VPS placement into a reoperative abdomen from 2009-2019. Clinical data were collected, and patients undergoing laparoscopy (LAP) were compared to those undergoing an open approach (OPEN)., Results: A total of 120 children underwent 169 VPS placements at a median age of 8 y (IQR 2-15 y), and a mean number of two prior abdominal operations (IQR 1-2). Laparoscopy was used in 24% of cases. Shunt-related complications within 30 d were lower in the LAP group (0% versus 19%, P = 0.001), as were VPS-related postoperative emergency department visits (0% versus 13%, P = 0.003) and readmissions (0% versus 13%, P = 0.013). Shunt malfunction rates were higher (42% OPEN versus 25% LAP, P = 0.03) and occurred sooner in the OPEN group (median 26 versus 78 wk, P = 0.01). The LAP group demonstrated shorter operative times (63 versus 100 min, P < 0.0001), and the only bowel injury. Time to feeds, length of stay, and mortality were similar between groups., Conclusions: Laparoscopic guidance during VPS placement into the reoperative abdomen is associated with a decrease in shunt-related complications, longer shunt patency, and shorter operative times. Prospective study may clarify the potential benefits of laparoscopy in this setting., (Published by Elsevier Inc.)

Objective: The middle fossa transpetrosal approach to the petroclival and posterior cavernous sinus regions includes removal of the anterior petrous apex (APA), an area well studied in adults but not in children. To this end, the authors performed a morphometric analysis of the APA region during pediatric maturation., Methods: Measurements of the distance from the clivus to the internal auditory canal (IAC; C-IAC), the distance of the petrous segment of the internal carotid artery (petrous carotid; PC) to the mesial petrous bone (MPB; PC-MPB), the distance of the PC to the mesial petrous apex (MPA; PC-MPA), and the IAC depth from the middle fossa floor (IAC-D) were made on thin-cut CT scans from 60 patients (distributed across ages 0-3, 4-7, 8-11, 12-15, 16-18, and > 18 years). The APA volume was calculated as a cylinder using C-IAC (length) and PC-MPB (diameter). APA pneumatization was noted. Data were analyzed by laterality, sex, and age., Results: APA parameters did not differ by laterality or sex. APA pneumatization was seen on 20 of 60 scans (33.3%) in patients ≥ 4 years. The majority of the APA region growth occurred by ages 8-11 years, with PC-MPA and PC-MPB increasing 15.9% (from 9.4 to 10.9 mm, p = 0.08) and 23.5% (from 8.9 to 11.0 mm, p < 0.01) between ages 0-3 and 8-11 years, and C-IAC increasing 20.7% (from 13.0 to 15.7 mm, p < 0.01) between ages 0-3 and 4-7 years. APA volume increased 79.6% from ages 0-3 to 8-11 years (from 834.3 to 1499.2 mm3, p < 0.01). None of these parameters displayed further significant growth. Finally, IAC-D increased 51.1% (from 4.3 to 6.5 mm, p < 0.01) between ages 0-3 and adult, without significant differences between successive age groups., Conclusions: APA development is largely complete by the ages of 8-11 years. Knowledge of APA growth patterns may aid approach selection and APA removal in pediatric patients.

Objective: Children with nonoperative brain tumors, such as diffuse intrinsic pontine gliomas (DIPGs), often have life-threatening hydrocephalus. Palliative shunting is common in such cases but can be complicated by hardware infection and mechanical failure. Endoscopic third ventriculostomy (ETV) is a minimally invasive alternative to treat hydrocephalus without implanted hardware. Herein, the authors report their institutional experience with palliative ETV for primary pediatric brain tumors., Methods: The authors conducted a retrospective review of consecutive patients who had undergone palliative ETV for hydrocephalus secondary to nonresectable primary brain tumors over a 10-year period at Rady Children's Hospital. Collected variables included age, sex, tumor type, tumor location, presence of leptomeningeal spread, use of a robot for ETV, complications, ETV Success Score (ETVSS), functional status, length of survival, and follow-up time. A successful outcome was defined as an ETV performed without clinically significant perioperative complications or secondary requirement for a new shunt., Results: Fifteen patients met the study inclusion criteria (11 males, 4 females; average age 7.9 years, range 0.8-21 years). Thirteen patients underwent manual ETV, and 2 patients underwent robotic ETV. Preoperative symptoms included gaze palsy, nausea/vomiting, headache, lethargy, hemiparesis, and seizures. Tumor types included DIPG (3), intraventricular/thalamic glioblastoma (2), and leptomeningeal spread of medulloblastoma (2), anaplastic oligo-/astrocytoma (2), rhabdoid tumor (2), primitive neuroectodermal tumor (1), ganglioglioma (1), pineoblastoma (1), and embryonal carcinoma (1). The mean preoperative ETVSS was 79 ± 8.8. There was 1 perioperative complication, a wound breakdown consistent with refractory hydrocephalus. The mean follow-up was 4.9 ± 5.5 months overall, and mean survival for the patients who died was 3.2 ± 3.6 months. Two patients remained alive at a mean follow-up of 15.7 months. Palliative ETV was successful in 7 patients (47%) and unsuccessful in 8 (53%). While patients with successful ETV were significantly older (11.9 ± 5.6 vs 4.4 ± 4.1 years, p = 0.010), there were no significant differences in preoperative ETVSS (p = 0.796) or postoperative survival (p = 0.476) between the successful and unsuccessful groups. Overall, functional outcomes were similar between the two groups; there was no significant difference in posttreatment Karnofsky Performance Status scores (68.6 ± 19.5 vs 61.3 ± 16.3, p = 0.454), suggesting that including ETV in the treatment algorithm did not worsen outcomes., Conclusions: Palliative ETV is a safe and potentially efficacious treatment option in selected pediatric patients with hydrocephalus from nonoperative brain tumors. Close follow-up, especially in younger children, is required to ensure that patients with refractory symptoms receive appropriate secondary CSF diversion.

Objective: We describe our single-institutional experience with magnetic resonance-guided stereotactic laser ablation (SLA) for the treatment of newly diagnosed and recurrent pediatric brain tumors., Methods: Eighteen consecutive ablation procedures were performed in 17 patients from March 2016-April 2020. Patient demographics, indications, procedures, neuroimaging features, and outcomes were reviewed retrospectively., Results: Seventeen patients (mean age of 11.4 years, 11 boys, 6 girls) underwent SLA with a mean follow-up of 24 months (range: 3-45 months). Tumor histologies included pilocytic astrocytoma (n = 5), ganglioglioma (n = 3), low-grade glioma not otherwise specified (n = 4), glioblastoma (n = 2), meningioma (n = 1), medulloblastoma (n = 1), and metastatic malignant peripheral nerve sheath tumor (n = 1). SLA was first-line therapy in 10 patients. Mean procedure duration including anesthesia time was 328 minutes (range: 244-529 minutes), and mean postoperative length of stay was 1.5 days (range 1-5 days). The complication rate was 29%, which included 3 patients who experienced postoperative motor changes, which resolved within several weeks of surgery, 1 patient with self-limited intraoperative bradycardia and hypotension, and 1 patient who died postoperatively due to intracranial hemorrhage from a distant lesion. Twelve of 17 patients had a neuroimaging response after SLA (4 complete responses, 8 partial responses, 1 stable disease). Percentage of tumor shrinkage from baseline ranged from 33%-100% (mean 75%). Patients with low-grade glioma exhibited the best responses to SLA (range 3%-100% decrease; mean 90%; 36% complete response rate)., Conclusions: SLA is a minimally invasive modality for the treatment of newly diagnosed and recurrent low-grade pediatric brain tumors. Low-grade glioma exhibited the best responses. Identification of ideal candidates for SLA, mitigation of perioperative complications, and demonstration of long-term outcomes need to be better defined in a clinical trial setting., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Compared to adult AVMs, there is a paucity of data on the microsurgical treatment of pediatric AVMs. We report our institutional experience with pediatric AVMs treated by microsurgical resection with or without endovascular embolization and radiation therapy., Methods: We retrospectively reviewed all patients ≤ 18 years of age with cerebral AVMs that underwent microsurgical resection at Rady Children's Hospital 2002-2019., Results: Eighty-nine patients met inclusion criteria. The mean age was 10.3 ± 5.0 years, and 56% of patients were male. In total, 72 (81%) patients presented with rupture. Patients with unruptured AVMs presented with headache (n = 5, 29.4%), seizure (n = 9, 52.9%), or incidental finding (n = 3, 17.7%). The mean presenting mRS was 2.8 ± 1.8. AVM location was lobar in 78%, cerebellar/brainstem in 15%, and deep supratentorial in 8%. Spetzler-Martin grade was I in 28%, II in 45%, III in 20%, IV in 6%, and V in 1%. Preoperative embolization was utilized in 38% of patients and more frequently in unruptured than ruptured AVMs (62% vs. 32%, p = 0.022). Radiographic obliteration was achieved in 76/89 (85.4%) patients. Complications occurred in 7 (8%) patients. Annualized rates of delayed rebleeding and recurrence were 1.2% and 0.9%, respectively. The mean follow-up was 2.8 ± 3.1 years. A good neurological outcome (mRS score ≤ 2) was obtained in 80.9% of patients at last follow-up and was improved relative to presentation for 75% of patients., Conclusions: Our case series demonstrates high rates of radiographic obliteration and relatively low incidence of neurologic complications of treatment or AVM recurrence.

Background: Removal of the anterior clinoid process (ACP) can expand anterior skull base surgical corridors. ACP development and anatomical variations are poorly defined in children., Objective: To perform a morphometric analysis of the ACP during pediatric maturation., Methods: Measurements of ACP base thickness (ACP-BT), midpoint thickness (ACP-MT), length (ACP-L), length from optic strut to ACP tip (ACP-OS), pneumatization (ACP-pneumo), and the presence of an ossified carotico-clinoid ligament (OCCL) or interclinoid ligament (OIL) were made from high-resolution computed-tomography scans from 60 patients (ages 0-3, 4-7, 8-11 12-15, 16-18, and >18 yr). Data were analyzed by laterality, sex, and age groups using t-tests and linear regression., Results: There were no significant differences in ACP parameters by laterality or sex, and no significant growth in ACP-BT or ACP-MT during development. From ages 0-3 yr to adult, mean ACP-L increased 49%, from 7.7 to 11.5 mm. The majority of ACP-L growth occurred in 2 phases between ages 0-3 to 8-11 and ages 16-18 to adult. Conversely, ACP-OS was stable from ages 0-3 to 8-11 but increased by 63% between ages 8-11 to adult. Variations in ACP morphology (OCCL/OIL/ACP-pneumo) were found in 15% (9/60) of scans. OCCL and OIL occurred in patients as young as 3 yrs, whereas ACP-pneumo was not seen in patients younger than 11 yrs., Conclusion: The ACP demonstrates stable thickness and a complex triphasic elongation and remodeling pattern with development, the understanding of which may facilitate removal in patients <12. Clinically relevant ACP anatomic variations can occur at any age., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Biopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors., Methods: A retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children's Hospital in San Diego between December 2015 and January 2020., Results: The ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%., Conclusions: Robot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

Background: Upper airway obstruction leading to dyspnea and dysphagia after occipitocervical fusion is a rare complication that has significant morbidity., Objective: To estimate the frequency of postoperative dyspnea and dysphagia in children after occipitocervical fusion and to identify variables associated with its occurrence., Methods: We retrospectively reviewed outcomes from all pediatric occipitocervical fusions at our institution between 2007 and 2014. Pre- and postoperative computed tomography (CT) scans were compared to determine differences in the clivoaxial (OC2) angles., Results: Sixty-seven pediatric patients underwent occipitocervical fusions. Median age was 9.6 yr (range 6 mo-18 yr). Fifty-six of 62 patients (90.3%) with at least 1 yr of follow-up had successful fusions. Eleven had pre-existing symptoms or otherwise compromised examination (eg, severe traumatic brain injury). None of 15 patients placed in extension (>2 degrees) relative to preoperative CT in Situ position developed new dyspnea or dysphagia. Nine of forty patients (23%) kept in Situ or flexed position developed new symptoms of dyspnea or dysphagia. Dysphagia in patients fused in the in Situ position was milder and resolved within a few weeks. No patient under age 5 (n = 20) developed symptoms of dyspnea or dysphagia regardless of head position. There were 3 cases of infection, 1 clinically silent vertebral artery injury, and 3 deaths at last follow-up., Conclusion: Positioning of the child's head prior to occipitocervical fusion has considerable impact on outcomes, especially in older children. Careful measurements of the OC2 angle during surgery to ensure optimal head positioning in Situ or slightly extended position may prevent postoperative dysphagia or dyspnea., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation is challenging. To better understand common genetic variation associated with brain diseases, we defined noncoding regulatory regions for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with variants in transcriptional enhancers and promoters in neurons, sporadic Alzheimer's disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting disease-risk variants in cell-type-specific enhancers to promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia, but not in neurons or astrocytes. These findings revise and expand the list of genes likely to be influenced by noncoding variants in AD and suggest the probable cell types in which they function., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: Lesions of the foramen magnum, inferolateral-to-midclival areas, and ventral pons and medulla are often treated using a far-lateral or extreme-lateral infrajugular transcondylar-transtubercular exposure (ELITE) approach. The development and surgical relevance of critical posterior skull base bony structures encountered during these approaches, including the occipital condyle (OC), hypoglossal canal (HGC), and jugular tubercle (JT), are nonetheless poorly defined in the pediatric population., Methods: Measurements from high-resolution CT scans were made of the relevant posterior skull base anatomy (HGC depth from posterior edge of the OC, OC and JT dimensions) from 60 patients (evenly distributed among ages 0-3, 4-7, 8-11, 12-15, 16-18, and > 18 years), and compared between laterality, sex, and age groups by using t-tests and linear regression., Results: There were no significant differences in posterior skull base parameters by laterality, and HGC depth and JT size did not differ by sex. The OC area was significantly larger in males versus females (174.3 vs 152.2 mm2; p = 0.01). From ages 0-3 years to adult, the mean HGC depth increased 27% (from 9.0 to 11.4 mm) and the OC area increased 52% (from 121.4 to 184.0 mm2). The majority of growth for these parameters occurred between the 0-3 year and 4-7 year age groups. Conversely, JT volume increased nearly 3-fold (281%) from 97.4 to 370.9 mm3 from ages 0-3 years to adult, with two periods of substantial growth seen between the 0-3 to 4-7 year and the 12-15 to 16-18 year age groups. Overall, JT growth during pediatric development was significantly greater than increases in HGC depth and OC area (p < 0.05). JT volume remained < 65% of adult size up to age 16., Conclusions: When considering a far-lateral or ELITE approach in pediatric patients, standard OC drilling is likely to be needed due to the relative stability of OC and HGC anatomy during development. The JT significantly increases in size with development, yet is only likely to need to be drilled in older children (> 16 years) and adults.

Background: Nonlesional cingulate gyrus epilepsy is rare, difficult to diagnose, and challenging to treat., Methods: We report the use of ROSA (Medtech Surgical, Inc., New York, NY, USA) robotic assistance for stereotactic EEG (S-EEG) localization and therapeutic thermal laser ablation of a nonlesional cingulate gyrus epileptogenic zone in a 17-year-old female with intractable partial epilepsy., Results: After an inconclusive exhaustive initial workup, robotic-assisted S-EEG localized the patient's seizure focus to the right cingulate gyrus. Robotic-assisted lesioning of the cingulate gyrus was performed via 5 total ablations with 3 minimally invasive catheters. There were no perioperative complications. The patient was discharged home on postoperative day 2 at her neurologic baseline. She was seizure free for 8 months postoperatively, with a sustained partial response through the 23-month follow-up., Conclusions: This report expands the technical uses, pathologies, and patient populations being treated via robotic-assisted neurosurgery., (© 2019 S. Karger AG, Basel.)

OBJECTIVE Treatment of hemorrhagic cavernous malformations within the lateral pontine region demands meticulous surgical planning and execution to maximize resection while minimizing morbidity. The authors report a single institution's experience using the extended middle fossa rhomboid approach for the safe resection of hemorrhagic cavernomas involving the lateral pons. METHODS A retrospective chart review was performed to identify and review the surgical outcomes of patients who underwent an extended middle fossa rhomboid approach for the resection of hemorrhagic cavernomas involving the lateral pons during a 10-year period at Rady Children's Hospital of San Diego. Surgical landmarks for this extradural approach were based on the Fukushima dual-fan model, which defines the rhomboid based on the following anatomical structures: 1) the junction of the greater superficial petrosal nerve (GSPN) and mandibular branch of the trigeminal nerve; 2) the lateral edge of the porus trigeminus; 3) the intersection of the petrous ridge and arcuate eminence; and 4) the intersection of the GSPN, geniculate ganglion, and arcuate eminence. The boundaries of maximal bony removal for this approach are the clivus inferiorly below the inferior petrosal sinus; unroofing of the internal auditory canal posteriorly; skeletonizing the geniculate ganglion, GSPN, and internal carotid artery laterally; and drilling under the Gasserian ganglion anteriorly. This extradural petrosectomy allowed for an approach to all lesions from an area posterolateral to the basilar artery near its junction with cranial nerve (CN) VI, superior to the anterior inferior cerebellar artery and lateral to the origin of CN V. Retraction of the mandibular branch of the trigeminal nerve during this approach allowed avoidance of the region involving CN IV and the superior cerebellar artery. RESULTS Eight pediatric patients (4 girls and 4 boys, mean age of 13.2 ± 4.6 years) with hemorrhagic cavernomas involving the lateral pons and extension to the pial surface were treated using the surgical approach described above. Seven cavernomas were completely resected. In the eighth patient, a second peripheral lesion was not resected with the primary lesion. One patient had a transient CN VI palsy, and 2 patients had transient trigeminal hypesthesia/dysesthesia. One patient experienced a CSF leak that was successfully treated by oversewing the wound. CONCLUSIONS The extended middle fossa approach can be used for resection of lateral pontine hemorrhagic cavernomas with minimal morbidity in the pediatric population.

Normal and pathologic cells secrete extracellular vesicles (EV), which are defined as 30-2,000 nm spherical organelles. It has been found that EV mediate various biological functions including cellular remodeling and export of biomolecules, extracellular communication, immune stimulation and suppression, and modulation of the cellular microenvironment. EV secreted by human glioma cells contain a wealth of tumor-specific proteins and nucleic acids that can be isolated from patients with these neoplasms. Thus, EV contribute to the development of biomarkers, and additionally have certain therapeutic potential for possible use in neuro-oncology and neurosurgery., (© 2018 S. Karger AG, Basel.)

OBJECTIVE Endoscopic third ventriculostomy (ETV) is a surgical alternative to placing a CSF shunt in certain patients with hydrocephalus. The ETV Success Score (ETVSS) is a reliable, simple method to estimate the success of the procedure by 6 months of postoperative follow-up. The highest score is 90, estimating a 90% chance of the ETV effectively treating hydrocephalus without requiring a shunt. Treatment with ETV fails in certain patients, despite their being the theoretically best candidates for the procedure. In this study the authors attempted to identify factors that further predicted success in patients with the highest ETVSSs. METHODS A retrospective review was performed of all patients treated with ETV at 3 institutions. Demographic, radiological, and clinical data were recorded. All patients by definition were older than 1 year, had obstructive hydrocephalus, and did not have a prior shunt. Failure of ETV was defined as the need for a shunt by 1 year. The ETV was considered a success if the patient did not require another surgery (either shunt placement or a repeat endoscopic procedure) by 1 year. A statistical analysis was performed to identify factors associated with success or failure. RESULTS Fifty-nine patients met the entry criteria for the study. Eleven patients (18.6%) required further surgery by 1 year. All of these patients received a shunt. The presenting symptom of lethargy statistically correlated with success (p = 0.0126, odds ratio [OR] = 0.072). The preoperative radiological finding of transependymal flow (p = 0.0375, OR 0.158) correlated with success. A postoperative larger maximum width of the third ventricle correlated with failure (p = 0.0265). CONCLUSIONS The preoperative findings of lethargy and transependymal flow statistically correlated with success. This suggests that the best candidates for ETV are those with a relatively acute elevation of intracranial pressure. Cases without these findings may represent the failures in this highly selected group.

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Management of patients afflicted with brain metastasis requires tailoring of therapeutic strategies based on survival expectations. Therefore, the development of prognostic indices is of critical importance in this patient population., Objective: To determine whether the cumulative intracranial tumor volume (CITV) of brain metastasis augments the prognostic value of the lung-specific Graded Prognostic Assessment (GPA) index., Methods: Patient data were derived from 365 lung cancer patients with brain metastasis who were consecutively treated with stereotactic radiosurgery at the University of California, San Diego/San Diego Gamma Knife Center. CITV was analyzed to determine the volume cutoff that maximized sensitivity and specificity for 1-year survival. Multivariate Cox proportional hazard modeling was performed, and overall survival was estimated by the Kaplan-Meier method risk stratifying with or without this optimal CITV. The prognostic value of these models (lung-specific GPA ± CITV) was quantitatively compared with the use of net reclassification improvement (>0) and integrated discrimination improvement., Results: For the University of California, San Diego/San Diego Gamma Knife Center cohort, the CITV cutoff that had the greatest survival discrimination at 1 year was 4 cm. The addition of CITV to the lung-specific GPA indexes significantly improved the prognostic value of lung-specific GPA, with net reclassification improvement >0 of 0.430 (95% confidence interval, 0.228-0.629) and integrated discrimination improvement of 0.029 (95% confidence interval, 0.004-0.073). These findings were validated in an independent cohort of 1638 lung cancer patients with brain metastasis who were treated with stereotactic radiosurgery at the Katsuta Hospital Mito Gamma House in Japan., Conclusion: In independent cohorts, the addition of CITV to the lung-specific GPA index significantly improved the prognostic value of this index., Abbreviations: AUC, area under the receiver-operating characteristic curveBM, brain metastasisCITV, cumulative intracranial tumor volumeds-GPA, disease-specific Graded Prognostic AssessmentGPA, Graded Prognostic AssessmentIDI, integrated discrimination improvementKHMGH, Katsuta Hospital Mito Gamma HouseKPS, Karnofsky Performance StatusNRI, net reclassification improvementROC, receiver-operating characteristic curveSRS, stereotactic radiosurgeryUCSD/SDGKC, University of California, San Diego/San Diego Gamma Knife Center.

Object: Low-molecular-weight heparins (LMWHs), mainly enoxaparin, offer several advantages over standard anticoagulation therapies such as unfractionated heparin and warfarin, including predictable pharmacokinetics, minimal monitoring, and subcutaneous administration. The purpose of this study was to determine the safety and efficacy of LMWHs in pediatric neurosurgical patients., Methods: A retrospective study was performed with patients 18 years old or younger who were admitted to the Pediatric Neurosurgery Service at Texas Children's Hospital and treated with LMWH for either therapeutic or prophylactic purposes between March 1, 2011, and December 30, 2013. Demographic and clinical features and outcomes were recorded., Results: LMWH was administered for treatment of venous thromboembolic events (VTEs) in 17 children and for prophylaxis in 24 children. Clinical resolution of VTEs occurred in 100% (17 of 17) of patients receiving therapeutic doses of LMWH. No patient receiving prophylactic doses of LMWH developed a new VTE. Major or minor bleeding complications occurred in 18% (3 of 17 children) and 4% (1 of 24 children) of those receiving therapeutic and prophylactic doses, respectively. All 4 patients who experienced hemorrhagic complications had other bleeding risk factors-i.e., coagulopathies and antiplatelet medications., Conclusions: LMWH seems to be safe and efficacious for both management and prophylaxis of VTEs in pediatric neurosurgery. However, pediatric practitioners should be aware of higher risk for bleeding complications with increasing doses of LMWH, especially in patients with preexisting bleeding disorders or concurrent use of antiplatelet agents.

Object: This study was designed to assess the relationship between insurance status and likelihood of receiving a neurosurgical procedure following admission for either extraaxial intracranial hemorrhage or spinal vertebral fracture., Methods: A retrospective analysis of the Nationwide Inpatient Sample (NIS; 1998-2009) was performed. Cases of traumatic extraaxial intracranial hematoma and spinal vertebral fracture were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Within this cohort, those patients receiving a craniotomy or spinal fusion and/or decompression in the context of an admission for traumatic brain or spine injury, respectively, were identified using the appropriate ICD-9 procedure codes., Results: A total of 190,412 patients with extraaxial intracranial hematoma were identified between 1998 and 2009. Within this cohort, 37,434 patients (19.7%) received a craniotomy. A total of 477,110 patients with spinal vertebral fracture were identified. Of these, 37,302 (7.8%) received a spinal decompression and/or fusion. On multivariate analysis controlling for patient demographics, severity of injuries, comorbidities, hospital volume, and hospital characteristics, uninsured patients had a reduced likelihood of receiving a craniotomy (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.71-0.82) and spinal fusion (OR 0.67, 95% CI 0.64-0.71) relative to insured patients. This statistically significant trend persisted when uninsured and insured patients were matched on the basis of mortality propensity score. Uninsured patients demonstrated an elevated risk-adjusted mortality rate relative to insured patients in cases of extraaxial intracranial hematoma. Among patients with spinal injury, mortality rates were similar between patients with and without insurance., Conclusions: In this study, uninsured patients were consistently less likely to receive a craniotomy or spinal fusion for traumatic intracranial extraaxial hemorrhage and spinal vertebral fracture, respectively. This difference persisted after accounting for overall injury severity and patient access to high- or low-volume treatment centers, and potentially reflects a resource allocation bias against uninsured patients within the hospital setting. This information adds to the growing literature detailing the benefits of health reform initiatives seeking to expand access for the uninsured.

Study Design: Cross-sectional analysis of the American College of Surgeons' National Surgical Quality Improvement Program database between 2005 and 2011., Objective: To determine whether differences exist in 30-day rate of return to the operating room, mortality, and other perioperative outcomes for spinal fusion by specialty., Summary of Background Data: Although both neurosurgeons and orthopedic surgeons perform spinal fusions, it is unclear whether surgeon specialty impacts perioperative outcomes., Methods: Unadjusted bivariate analysis was performed to determine whether outcomes differed by surgeon specialty. A Bonferroni correction was applied to account for multiple comparisons. For outcomes with a statistically significant association, further multivariate analysis was performed., Results: A total of 9719 patients receiving a spinal fusion were identified. Of them, 54.0% had their operation completed by a neurosurgeon. Orthopedic surgeons had practices with a greater percentage of lumbar spine cases (76.0% vs. 65.0%, P < 0.001). There was not a statistically significant difference in the number of levels fused or operative technique used between specialties. There was no difference in the majority of perioperative outcomes between orthopedic surgeons and neurosurgeons including death, rate of return to the operating room, and other complications associated with significant morbidity. On unadjusted analysis, it was found that neurosurgeons were associated with a decreased incidence of operations requiring blood transfusion relative to orthopedic surgeons (8.3% vs. 14.6%, P < 0.001). This trend persisted on multivariate analysis controlling for preoperative hematocrit, history of bleeding disorder, anatomical location of the operation, number of levels fused, operative technique, demographics, and comorbidities (odds ratio, 0.49; 95% confidence interval, 0.43-0.57)., Conclusion: Spine surgeons, regardless of specialty, seem to achieve equivalent outcomes on measured metrics of mortality, 30-day readmission, and surgical site infection. Observed differences in blood transfusion rates by specialty were noted, but the cause of this difference is unclear and warrants further investigation to assess the impact of this difference, if any, on patient outcomes and cost., Level of Evidence: 3.

Upper airway obstruction resulting from overflexion of the craniocervical junction after occipitocervical fusion is a rare but potentially life-threatening complication and is associated with morbidity. The authors retrospectively reviewed the medical records and diagnostic images of 2 pediatric patients who underwent occipitocervical fusion by the Neuro-Spine Program at Texas Children's Hospital and experienced dyspnea and/or dysphagia from new upper airway obstruction in the postoperative period. Patient demographics, operative data, and preoperative and postoperative occiput-C2 angles were recorded. A review of the literature for similar complications after occipitocervical fusion was performed. A total of 13 cases of prolonged upper airway obstruction after occipitocervical fusion were analyzed. Most of these cases involved adults with rheumatoid arthritis. To the best of the authors' knowledge, there have been no previous reports of prolonged upper airway obstruction in children after an occipitocervical fusion. Fixation of the neck in increased flexion (-18° to -5°) was a common finding among these adult and pediatric cases. The authors' cases involved children with micrognathia and comparatively large tongues, which may predispose the oropharynx to obstruction with even the slightest amount of increased flexion. Close attention to a satisfactory fixation angle (occiput-C2 angle) is necessary to avoid airway obstruction after an occipitocervical fusion. Children with micrognathia are particularly sensitive to changes in flexion at the craniocervical junction after occipitocervical fixation.

Intramedullary spinal cord hematomas are a rare neurosurgical pathological entity typically arising from vascular and neoplastic lesions. Endometriosis is an extremely rare cause of intramedullary spinal cord hematoma, with only 5 previously reported cases in the literature. Endometriosis is characterized by ectopic endometrial tissue, typically located in the female pelvic cavity, that causes a cyclical pain syndrome, bleeding, and infertility. In the rare case of intramedullary endometriosis of the spinal cord, symptoms include cyclical lower-extremity radiculopathies and voiding difficulties, and can acutely cause cauda equina syndrome. The authors report a case of endometriosis of the conus medullaris, the first to include radiological, intraoperative, and histopathological imaging. A brief review of the literature is also presented, with discussion including etiological theories surrounding intramedullary endometriosis.

Object: Using a database that enabled longitudinal follow-up, the authors assessed the long-term outcomes of unruptured cerebral aneurysms repaired by clipping or coiling., Methods: An observational analysis of the California Office of Statewide Health Planning and Development (OSHPD) database, which follows patients longitudinally in time and through multiple hospitalizations, was performed for all patients initially treated for an unruptured cerebral aneurysm in the period from 1998 to 2005 and with follow-up data through 2009., Results: Nine hundred forty-four cases (36.5%) were treated with endovascular coiling, 1565 cases (60.5%) were surgically clipped, and 76 cases were treated with both coiling and clipping. There was no significant difference in any demographic variable between the two treatment groups except for age (median: 55 years for the clipped group, 58 years for the coiled group, p < 0.001). Perioperative (30-day) mortality was 1.1% in patients with coiled aneurysms compared with 2.3% in those with clipped aneurysms (p = 0.048). The median follow-up was 7 years (range 4-12 years). At the last follow-up, 153 patients (16.2%) in the coiled group had died compared with 244 (15.6%) in the clipped group (p = 0.693). The adjusted hazard ratio for death at the long-term follow-up was 1.14 (95% CI 0.9-1.4, p = 0.282) for patients with endovascularly treated aneurysms. The incidence of intracranial hemorrhage was similar in the two treatment groups (5.9% clipped vs 4.8% coiled, p = 0.276). One hundred ninety-three patients (20.4%) with coiled aneurysms underwent additional hospitalizations for aneurysm repair procedures compared with only 136 patients (8.7%) with clipped aneurysms (p < 0.001). Cumulative hospital costs per patient for admissions involving aneurysm repair procedures were greater in the clipped group (median cost $98,260 vs $81,620, p < 0.001) through the follow-up., Conclusions: For unruptured cerebral aneurysms, an observed perioperative survival advantage for endovascular coiling relative to that for surgical clipping was lost on long-term follow-up, according to data from an administrative database of patients who were not randomly allocated to treatment type. A cost advantage of endovascular treatment was maintained even though endovascularly treated patients were more likely to undergo subsequent hospitalizations for additional aneurysm repair procedures. Rates of aneurysm rupture following treatment were similar in the two groups.

Object: Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection., Methods: The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions., Results: A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20-1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06-2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20-2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84-8.18)., Conclusions: Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

Object: There is limited information on the relationship between patient age and the clinical benefit of resection in patients with glioblastoma. The purpose of this study was to use a population-based database to determine whether patient age influences the frequency that gross-total resection (GTR) is performed, and also whether GTR is associated with survival difference in different age groups., Methods: The authors identified 20,705 adult patients with glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) registry (1998-2009). Surgical practice patterns were defined by the categories of no surgery, subtotal resection (STR), and GTR. Kaplan-Meier and multivariate Cox regression analyses were used to assess the pattern of surgical practice and overall survival., Results: The frequency that GTR was achieved in patients with glioblastoma decreased in a stepwise manner as a function of patient age (from 36% [age 18-44 years] to 24% [age ≥ 75]; p < 0.001). For all age groups, glioblastoma patients who were selected for and underwent GTR showed a 2- to 3-month improvement in overall survival (p < 0.001) relative to those who underwent STR. These trends remained true after a multivariate analysis that incorporated variables including ethnicity, sex, year of diagnosis, tumor size, tumor location, and radiotherapy status., Conclusions: Gross-total resection is associated with improved overall survival, even in elderly patients with glioblastoma. As such, surgical decisions should be individually tailored to the patient rather than an adherence to age as the sole clinical determinant.

To determine whether immediate post-operative brachytherapy can be safely applied to newly diagnosed glioblastomas to retard tumor progression prior to initiation of external beam radiation therapy (EBRT) and temozolomide. Between 1996 and 2011, eleven patients underwent implantation of GliaSite (n = 9) or MammoSite (n = 2) at the time of surgical resection. Brachytherapy was carried out on post-operative day 2-3, with 45-60 Gy delivered to a 1 cm margin. All patients underwent subsequent standard radiation/temozolomide treatment 4-5 weeks post-irradiation. There were no wound related complications. Toxicity was observed in two patients (2/11 or 18 %), including one post-operative seizure and one case of cerebral edema that resolved after a course of steroid treatment. Immediate post-operative and pre-irradiation/temozolomide magnetic resonance imaging assessment was available for 9 of the 11 patients. Two of these nine patients (22 %) developed new regions of contrast enhancement prior to irradiation/temozolomide. This compares favorably to historical data where 53 % of patient suffer such tumor progression. While there was a trend toward improved 6 month progression free survival in the brachytherapy/temozolomide/radiation treated patients, the overall survival of these patients were comparable to historical controls. This case series demonstrates the safety of immediate post-operative brachytherapy when applied prior to EBRT and temozolomide in the treatment of newly diagnosed glioblastomas.

Objectives: Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline., Design: Retrospective chart analysis., Setting: PICU in university-affiliated children's hospital., Patients: All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria., Intervention: Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed., Measurements and Main Results: Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001)., Conclusions: Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.

Background: Stereotactic brain biopsies are widely used for establishing the diagnosis of intracranial lesions. Here we examine whether stereotactic biopsy of smaller brain lesions, defined for this study as being less than 1 cubic centimeter (1 cc) in volume, are associated with lowered diagnostic yield., Methods: We conducted a retrospective analysis of 267 consecutive patients who underwent stereotactic brain biopsy between 2007 and 2011. Lesion volumes were calculated and were stratified by <1 or >1 cc., Results: A total of 13 of 246 (5.2%) biopsies for lesions >1 cc resulted in nondiagnostic tissue or an incorrect diagnosis. In contrast, 5 of 21 (23.8%) biopsies for <1 cc lesions yielded nondiagnostic or incorrect diagnosis. Posthoc review of tissue from the <1 cc lesions suggests the neuropathologist's expertise in the handling and analysis of limited specimen as a critical parameter of successful diagnosis. The operative morbidities were low for both the <1 and >1 cc biopsies (0% and 1%, respectively)., Conclusion: This study demonstrates that stereotactic cerebral biopsy of lesions less than a cubic centimeter in volume results in a lower diagnostic yield versus larger lesions (76.2% versus 94.8%). While auxiliary measures may be taken to improve diagnostic yield, these patients may be best managed in a specialized center with experienced stereotactic neurosurgeons and neuropathologists.

The discovery that tumor-derived proteins and nucleic acids can be detected in nano-sized vesicles in the plasma and cerebrospinal fluid of patients afflicted with brain tumors has expanded opportunities for biomarker and therapeutic discovery. Through delivery of their contents to surrounding cells, exosomes, microvesicles, and other nano-sized extracellular vesicles secreted by tumors modulate their environment to promote tumor growth and survival. In this review, we discuss the biological processes mediated by these extracellular vesicles and their applications in terms of brain tumor diagnosis, monitoring, and therapy. We review the normal physiology of these extracellular vesicles, their pertinence to tumor biology, and directions for research in this field.

Glioblastomas are among the most aggressive human cancers, and prognosis remains poor despite presently available therapies. Angiogenesis is a hallmark of glioblastoma, and the resultant vascularity is associated with poor prognosis. The proteins that mediate angiogenesis, including vascular endothelial growth factor (VEGF) signaling proteins, have emerged as attractive targets for therapeutic development. Since VEGF receptor-2 (VEGFR-2) is thought to be the primary receptor mediating angiogenesis, direct inhibition of this receptor may produce an ideal therapeutic effect. In this context, we tested the therapeutic effect of CT322, a selective inhibitor of VEGFR-2. Using an intracranial murine xenograft model (U87-EGFRvIII-luciferase), we demonstrate that CT322 inhibited glioblastoma growth in vivo and prolonged survival. Of note, the anti-neoplastic effect of CT322 is augmented by the incorporation of temozolomide or temozolomide with radiation therapy. Immunohistochemical analysis of CT322 treated tumors revealed decreased CD31 staining, suggesting that the tumoricidal effect is mediated by inhibition of angiogenesis. These pre-clinical results provide the foundation to further understand long term response and tumor escape mechanisms to anti-angiogenic treatments on EGFR over-expressing glioblastomas.

Background: Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who were not good candidates for surgical resection by either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS). Patients were excluded from ETV if they had a clinical history suggestive of non-obstructive hydrocephalus, including: (1) history of infection or ventricular hemorrhage and (2) leptomeningeal carcinomatosis. The rest of the patients were treated with VPS., Methods: We analyzed the clinical outcome of these patient cohorts, to determine whether the efficacy of VPS was compromised due to a history of infection, ventricular hemorrhage, or leptomeningeal carcinomatosis, and compared these results to those patients who underwent ETV., Results: Sixteen patients were treated with ETV and 36 patients were treated with VPS. The overall efficacy of symptomatic palliation was comparable in the ETV and VPS patients (ETV = 69%, VPS = 75%). In both groups, patients with more severe hydrocephalic symptoms such as nausea, vomiting, and lethargy were more likely to benefit from the procedure. The overall complication rate for the two groups was comparable (ETV = 12.6%, VPS = 19.4%), although the spectrum of complications differed. The overall survival, initial Karnofsky performance status (KPS), and three-month KPS, were similarly comparable (median survival: ETV 3 months, VPS 5.5 months; initial KPS: ETV = 66 ± 7, VPS = 69 ± 12; 3 months KPS: ETV = 86 ± 7, KPS = 84 ± 12)., Conclusion: VPS remains a reasonable option for poor RPA grade metastasis patients with hydrocephalus, even in the setting of a previous infection, hemorrhage, or in those with leptomeningeal disease. Optimal treatment of this population will involve the judicious consideration of the relative merits of VPS and ETV.