Search

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment., Significance: A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5., (©2023 American Association for Cancer Research.)

Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring. We highlight the importance of comprehensive collaboration to advance the understanding, diagnostics, and therapeutics for DMGs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Targeting tumor metabolism may improve the outcomes for patients with glioblastoma (GBM). To further preclinical efforts targeting metabolism in GBM, we tested the hypothesis that brain tumors can be stratified into distinct metabolic groups with different patient outcomes. Therefore, to determine if tumor metabolites relate to patient survival, we profiled the metabolomes of human gliomas and correlated metabolic information with clinical data. Results: We found that isocitrate dehydrogenase-wildtype (IDHwt) GBMs are metabolically distinguishable from IDH mutated (IDHmut) astrocytomas and oligodendrogliomas. Survival of patients with IDHmut gliomas was expectedly more favorable than those with IDHwt GBM, and metabolic signatures can stratify IDHwt GBMs subtypes with varying prognoses. Patients whose GBMs were enriched in amino acids had improved survival, while those whose tumors were enriched for nucleotides, redox molecules, and lipid metabolites fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data. Innovation: Our results suggest the existence of metabolic subtypes of GBM with differing prognoses, and further support the concept that metabolism may drive the aggressiveness of human gliomas. Conclusions: Our data show that metabolic signatures of human gliomas can inform patient survival. These findings may be used clinically to tailor novel metabolically targeted agents for GBM patients with different metabolic phenotypes. Antioxid. Redox Signal . 39, 942-956.

In this paper, we study the problem of inferring spatially-varying Gaussian Markov random fields (SV-GMRF) where the goal is to learn a network of sparse, context-specific GMRFs representing network relationships between genes. An important application of SV-GMRFs is in inference of gene regulatory networks from spatially-resolved transcriptomics datasets. The current work on inference of SV-GMRFs are based on the regularized maximum likelihood estimation (MLE) and suffer from overwhelmingly high computational cost due to their highly nonlinear nature. To alleviate this challenge, we propose a simple and efficient optimization problem in lieu of MLE that comes equipped with strong statistical and computational guarantees. Our proposed optimization problem is extremely efficient in practice: we can solve instances of SV-GMRFs with more than 2 million variables in less than 2 minutes. We apply the developed framework to study how gene regulatory networks in Glioblastoma are spatially rewired within tissue, and identify prominent activity of the transcription factor HES4 and ribosomal proteins as characterizing the gene expression network in the tumor peri-vascular niche that is known to harbor treatment resistant stem cells.

Development of spatial-integrative pre-clinical models is needed for glioblastoma, which are heterogenous tumors with poor prognosis. Here, we present an optimized protocol to generate three-dimensional ex vivo explant slice glioma model from orthotopic tumors, genetically engineered mouse models, and fresh patient-derived specimens. We describe a step-by-step workflow for tissue acquisition, dissection, and sectioning of 300-μm tumor slices maintaining cell viability. The explant slice model allows the integration of confocal time-lapse imaging with spatial analysis for studying migration, invasion, and tumor microenvironment, making it a valuable platform for testing effective treatment modalities. For complete details on the use and execution of this protocol, please refer to Comba et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities., Experimental Design: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs., Results: These studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed significant association of this transcriptional profile with worse overall survival and upregulation at recurrence. Notably, gene expression analyses identified upregulation of TGFβ signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Furthermore, THY1-positive cells represented <10% of cells in treatment-naïve tumors, compared to 75-96% in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model, which co-localized with macrophages within the perivascular niche. We then inhibited TGFBRI activity in vivo which decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors., Conclusions: These findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal cells within the perivascular niche., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment., (© 2022. The Author(s).)

Background: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources., Objective: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence., Methods: We used a fiber laser-based, label-free, nonconsumptive, high-resolution microscopy method (<60 seconds per 1 × 1 mm2), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of patients with skull base tumor. SRH images were then used to train a convolutional neural network model using 3 representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained convolutional neural network models were tested on a held-out, multicenter SRH data set., Results: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the 3 representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to segment tumor-normal margins and detect regions of microscopic tumor infiltration in meningioma SRH images., Conclusion: SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors' institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome., Methods: The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher's exact test. Multivariate analyses were performed using multivariate logistic regression., Results: Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1-2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR., Conclusions: The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

Mutant isocitrate-dehydrogenase 1 ( mIDH1 ) synthesizes the oncometabolite 2-hydroxyglutarate (2HG), which elicits epigenetic reprogramming of the glioma cells’ transcriptome by inhibiting DNA and histone demethylases. We show that the efficacy of immune-stimulatory gene therapy (TK/Flt3L) is enhanced in mIDH1 gliomas, due to the reprogramming of the myeloid cells’ compartment infiltrating the tumor microenvironment (TME). We uncovered that the immature myeloid cells infiltrating the mIDH1 TME are mainly nonsuppressive neutrophils and preneutrophils. Myeloid cell reprogramming was triggered by granulocyte colony-stimulating factor (G-CSF) secreted by mIDH1 glioma stem/progenitor-like cells. Blocking G-CSF in mIDH1 glioma–bearing mice restores the inhibitory potential of the tumor-infiltrating myeloid cells, accelerating tumor progression. We demonstrate that G-CSF reprograms bone marrow granulopoiesis, resulting in noninhibitory myeloid cells within mIDH1 glioma TME and enhancing the efficacy of immune-stimulatory gene therapy.

Glioblastomas (GBM) are the most common and aggressive tumors of the central nervous system. Rapid tumor growth and diffuse infiltration into healthy brain tissue, along with high intratumoral heterogeneity, challenge therapeutic efficacy and prognosis. A better understanding of spatiotemporal tumor heterogeneity at the histological, cellular, molecular, and dynamic levels would accelerate the development of novel treatments for this devastating brain cancer. Histologically, GBM is characterized by nuclear atypia, cellular pleomorphism, necrosis, microvascular proliferation, and pseudopalisades. At the cellular level, the glioma microenvironment comprises a heterogeneous landscape of cell populations, including tumor cells, non-transformed/reactive glial and neural cells, immune cells, mesenchymal cells, and stem cells, which support tumor growth and invasion through complex network crosstalk. Genomic and transcriptomic analyses of gliomas have revealed significant inter and intratumoral heterogeneity and insights into their molecular pathogenesis. Moreover, recent evidence suggests that diverse dynamics of collective motion patterns exist in glioma tumors, which correlate with histological features. We hypothesize that glioma heterogeneity is not stochastic, but rather arises from organized and dynamic attributes, which favor glioma malignancy and influences treatment regimens. This review highlights the importance of an integrative approach of glioma histopathological features, single-cell and spatially resolved transcriptomic and cellular dynamics to understand tumor heterogeneity and maximize therapeutic effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Comba, Faisal, Varela, Hollon, Al-Holou, Umemura, Nunez, Motsch, Castro and Lowenstein.)

Glioblastoma, the deadliest form of primary brain tumor, remains a disease without cure. Treatment resistance is in large part attributed to limitations in the delivery and distribution of therapeutic agents. Over the last 20 years, numerous preclinical studies have demonstrated the feasibility and efficacy of stem cells as antiglioma agents, leading to the development of trials to test these therapies in the clinic. In this review we present and analyze these studies, discuss mechanisms underlying their beneficial effect and highlight experimental progress, limitations and the emergence of promising new therapeutic avenues. We hope to increase awareness of the advantages brought by stem cells for the treatment of glioblastoma and inspire further studies that will lead to accelerated implementation of effective therapies.

Background: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect. We hypothesized that intraoperative stimulated Raman histology (SRH) and deep neural networks can be used to improve the intraoperative detection of glioma recurrence., Methods: We used fiber laser-based SRH, a label-free, nonconsumptive, high-resolution microscopy method (<60 sec per 1 × 1 mm2) to image a cohort of patients (n = 35) with suspected recurrent gliomas who underwent biopsy or resection. The SRH images were then used to train a convolutional neural network (CNN) and develop an inference algorithm to detect viable recurrent glioma. Following network training, the performance of the CNN was tested for diagnostic accuracy in a retrospective cohort (n = 48)., Results: Using patch-level CNN predictions, the inference algorithm returns a single Bernoulli distribution for the probability of tumor recurrence for each surgical specimen or patient. The external SRH validation dataset consisted of 48 patients (recurrent, 30; pseudoprogression, 18), and we achieved a diagnostic accuracy of 95.8%., Conclusion: SRH with CNN-based diagnosis can be used to improve the intraoperative detection of glioma recurrence in near-real time. Our results provide insight into how optical imaging and computer vision can be combined to augment conventional diagnostic methods and improve the quality of specimen sampling at glioma recurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors., Methods: A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas., Results: Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden ( P = .0055) and PTEN mutations ( P = .0235) negatively impacted survival, whereas IDH1 mutations positively impacted survival ( P < .0001). Clinical factors significantly associated with GBM survival included age ( P < .0001), preoperative Karnofsky Performance Scale score ( P = .0001), sex ( P = .0164), and clinical trial participation ( P < .0001). Higher preoperative T1-enhancing volume ( P = .0497) was associated with shorter survival. The ratio of TI-enhancing to nonenhancing disease (T1/T2 ratio) also significantly impacted survival ( P = .0022)., Conclusions: Our newly devised long-term survival - predictive nomogram based on clinical and genomic data can be used to advise patients regarding their potential outcomes and account for confounding factors in nonrandomized clinical trials., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data., Objective: To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection., Methods: We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression., Results: Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio = 2.5, 95% confidence interval: 1.8-3.4, P < .001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P < .001) and a lower rate of neurological complications (11% vs 20%, respectively, P = .018) than those who underwent intralesional resection., Conclusion: Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: Gastrostomy tube placement can temporarily seed the peritoneal cavity with bacteria and thus theoretically increases the risk of shunt infection when the two procedures are performed contemporaneously. The authors hypothesized that gastrostomy tube placement would not increase the risk of ventriculoperitoneal shunt infection. The object of this study was to test this hypothesis by utilizing a large patient cohort combined from multiple institutions., Methods: A retrospective study of all adult patients admitted to five institutions with a diagnosis of aneurysmal subarachnoid hemorrhage between January 2005 and January 2015 was performed. The primary outcome of interest was ventriculoperitoneal shunt infection. Variables, including gastrostomy tube placement, were tested for their association with this outcome. Standard statistical methods were utilized., Results: The overall cohort consisted of 432 patients, 47% of whom had undergone placement of a gastrostomy tube. The overall shunt infection rate was 9%. The only variable that predicted shunt infection was gastrostomy tube placement (p = 0.03, OR 2.09, 95% CI 1.07-4.08), which remained significant in the multivariate analysis (p = 0.04, OR 2.03, 95% CI 1.04-3.97). The greatest proportion of shunts that became infected had been placed more than 2 weeks (25%) and 1-2 weeks (18%) prior to gastrostomy tube placement, but the temporal relationship between shunt and gastrostomy was not a significant predictor of shunt infection., Conclusions: Gastrostomy tube placement significantly increases the risk of ventriculoperitoneal shunt infection.

Spinal laser interstitial thermal therapy (LITT) appears to be a promising novel modality for treatment of epidural metastatic spine disease in patients who are poor candidates for larger-scale oncologic spinal surgery and can act synergetically with spinal stereotactic radiosurgery to maximize local control and palliate pain. This technique is ideally suited for the intraoperative MRI suite to monitor the extent of the ablation in the epidural space. As percutaneous navigation, imaging, and LITT technology improve, broader applicability of this minimally invasive technique in spinal oncology is foreseen., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Patients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm., Methods: We conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission., Results: 311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2 cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission., Conclusions: Neurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2 cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Brain tumor biopsies that are routinely performed in clinical settings significantly aid in diagnosis and staging. The aim of this study is to develop and evaluate a methodological image-guided approach that would allow for routine sampling of glioma tissue from orthotopic mouse brain tumor models. A magnetic resonance imaging-guided biopsy method is presented to allow for spatially precise stereotaxic sampling of a murine glioma coupled with genome-scale technology to provide unbiased characterization of intra- and intertumoral clonal heterogeneity. Longitudinal and multiregional sampling of intracranial tumors allows for successful collection of tumor biopsy samples, thus allowing for a pathway-enrichment analysis and a transcriptional profiling of RNA sequencing data. Spatiotemporal gene expression pattern variations revealing genomic heterogeneity were found., Competing Interests: Disclosures: No disclosures to report. Conflict of Interest: None reported.

OBJECTIVE The aim of this paper is to compare the accuracy of the freehand technique versus the use of intraoperative guidance (either ultrasound guidance or frameless stereotaxy) for placement of parietooccipital ventricular catheters and to determine factors associated with reduced proximal shunt failure. METHODS This retrospective cohort study included all patients from 2 institutions who underwent a ventricular cerebrospinal fluid (CSF) shunting procedure in which a new parietooccipital ventricular catheter was placed between January 2005 and December 2013. Data abstracted for each patient included age, sex, method of ventricular catheter placement, side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision. Standard statistical methods were used for analysis. RESULTS A total of 257 patients were included in the study: 134 from the University of Michigan and 123 from Washington University in St. Louis. Accurate ventricular catheter placement was achieved in 81.2% of cases in which intraoperative guidance was used versus 67.3% when the freehand technique was used. Increasing age reduced the likelihood of accurate catheter placement (OR 0.983, 95% CI 0.971-0.995; p = 0.005), while the use of intraoperative guidance significantly increased the likelihood (OR 2.809, 95% CI 1.406-5.618; p = 0.016). During the study period, 108 patients (42.0%) experienced shunt failure, 79 patients (30.7%) had failure involving the proximal catheter, and 53 patients (20.6%) had distal failure (valve or distal catheter). Increasing age reduced the likelihood of being free from proximal shunt failure (OR 0.983, 95% CI 0.970-0.995; p = 0.008), while both the use of intraoperative guidance (OR 2.385, 95% CI 1.227-5.032; p = 0.011), and accurate ventricular catheter placement (OR 3.424, 95% CI 1.796-6.524; p = 0.009) increased the likelihood. CONCLUSIONS The use of intraoperative guidance during parietooccipital ventricular catheter placement as part of a CSF shunt system significantly increases the likelihood of accurate catheter placement and subsequently reduces the rate of proximal shunt failure.

OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

Background: Intraoperative angiography (IOA) is essential in evaluating residual aneurysm following clip ligation, but it does lead to an additional procedure which increases the duration of the procedure as well as increasing room traffic. We examined whether IOA during microsurgery is a risk factor for developing cranial surgical site infection., Materials and Methods: A retrospective cohort study was performed of all patients undergoing craniotomy for aneurysm treatment between 2005 and 2012 at the University of Michigan. IOA was used at the surgeons' discretion. The primary outcome of interest was occurrence of a surgical site infection and the secondary outcome of interest was clip repositioning following IOA. Variables including IOA were tested for their independent association with the occurrence of a surgical site infection., Results: During the study period 676 intracranial aneurysms were treated by craniotomy; IOA was used in 104 of these cases. There were a total of 20 surgical site infections, 2 in the IOA group (1.9%) and 18 in the non-IOA group (3.1%), indicating that IOA was not a statistically significant variable for infection (p=0.50). No additional single variable measured could be shown to have a statistically significant increase in infection, and there were no direct complications related to the use of IOA (stroke, dissection, perforation)., Conclusions: IOA does not increase the risk of developing a surgical site infection. It can be conducted without exposing patients to an undue risk of infection., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Endovascular treatment of small intracranial aneurysms has historically been technically challenging and has been associated with high rates of complications and intraprocedural rupture. In this study, we compared complication and recurrence rates for treatment of small aneurysms (≤ 4 mm) versus large aneurysms in the context of the advent of improvements in endovascular techniques and technologies., Methods: A retrospective cohort study was performed to include all patients who underwent coiling of an intracranial aneurysm between 2005 and 2012. Small aneurysms were defined as any aneurysm 4.0 mm or smaller in all dimensions. The primary outcome was a composite outcome of the occurrence of an intraoperative rupture or a perioperative thromboembolic event. The secondary outcome of interest was aneurysm recurrence., Results: During the study period, 483 patients were treated using endovascular techniques; 85 (17.6%) of these patients had small aneurysms. In the small aneurysm group, there was only one (1.2%) intraoperative rupture, three (3.5%) perioperative thromboembolic events, and 11 (12.9%) incidents of aneurysm recurrence. Both the primary and secondary outcomes of interest were similar in patients presenting with small or large aneurysms. Small aneurysm size was not a risk factor for either the composite primary outcome or aneurysm recurrence in multivariate analysis., Conclusions: Treatment of small intracranial aneurysms via conventional endovascular coiling techniques is not inferior to endovascular treatment of larger aneurysms based on our single institution experience. While technically challenging, such aneurysms may be treated safely and effectively with acceptable rates of complications and recurrence., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Craniocervical arterial dissections (CCADs) represent a preventable cause of acute ischemic stroke (AIS). Our objective was to describe clinical presentation, imaging features, treatment strategies, and report clinical and imaging outcomes of CCADs at a large pediatric tertiary referral center., Methods: Electronic medical records were queried using variations of the word dissection for patients under 25 years of age with neuroimaging over a 13-year period. Medical and imaging records were reviewed to identify carotid, vertebral, or intracranial dissections. Demographics, presenting symptoms, presence of AIS, mechanism of injury, dissection location, dissection treatment, and complications stemming from treatment were collected. Clinical outcome was classified according to modified Rankin Scale (mRS) score. Imaging follow-up was obtained until the dissection healed or stabilized., Results: A total 6,289 patients met initial search criteria. Of the 42 (0.7%) patients with CCADs, 23 (54.8%) had internal carotid artery (ICA) dissections, and 17 (40.5%) had vertebrobasilar (VB) dissections. More females had ICA dissections (p = 0.002), and more males had VB dissections (p = 0.01). CCADs associated with traumatic presentation occurred in 34 patients (81.0%), while 8 (19.0%) were spontaneous. Good outcomes (mRS 0-3) were noted for 36 patients, and 5 had poor outcomes (mRS 4-6). In the 17 patients with vessel occlusion, 50.0% had partial or complete recanalization at a mean follow-up of 23.9 months., Conclusions: CCAD is commonly related to trauma and presents with AIS. The majority of patients experience good clinical outcome. Recanalization of initial vessel occlusion occurs in half of cases at 2 years.

Object: Filum terminale lipomas (FTLs) are being identified with increasing frequency due to the increasing utilization of MRI. Although an FTL may be associated with tethered cord syndrome (TCS), in many cases FTLs are diagnosed incidentally in patients without any symptoms of TCS. The natural history of FTLs is not well defined., Methods: The authors searched the clinical and imaging records at a single institution over a 14-year interval to identify patients with FTLs. For patients with an FTL, the clinical records were reviewed for indication for imaging, presenting symptoms, perceived need for surgery, and clinical outcome. A natural history analysis was performed using all patients with more than 6 months of clinical follow-up., Results: A total of 436 patients with FTL were identified. There were 217 males and 219 females. Of these patients, 282 (65%) were adults and 154 (35%) were children. Symptoms of TCS were present in 22 patients (5%). Fifty-two patients underwent surgery for FTL (12%). Sixty-four patients (15%) had a low-lying conus and 21 (5%) had a syrinx. The natural history analysis included 249 patients with a mean follow-up time of 3.5 years. In the follow-up period, only 1 patient developed new symptoms., Conclusions: Filum terminale lipomas are a common incidental finding on spinal MRI, and most patients present without associated symptoms. The untreated natural history is generally benign for asymptomatic patients.

Object: Arachnoid cysts may occasionally be associated with subdural hygromas. The management of these concurrent findings is controversial., Methods: The authors reviewed their experience with arachnoid cysts and identified 8 patients with intracranial arachnoid cysts and an associated subdural hygroma. The medical records and images for these patients were also examined., Results: In total, 8 patients presented with concurrent subdural hygroma and arachnoid cyst. Of these 8 patients, 6 presented with headaches and 4 had nausea and vomiting. Six patients had a history of trauma. One patient was treated surgically at the time of initial presentation, and 7 patients were managed without surgery. All patients experienced complete resolution of their presenting signs and symptoms., Conclusions: Subdural hygroma may lead to symptomatic presentation for otherwise asymptomatic arachnoid cysts. The natural course of cyst-associated subdural hygromas, even when symptomatic, is generally benign, and symptom resolution can be expected in most cases. The authors suggest that symptomatic hygroma is not an absolute indication for surgical treatment and that expectant management can result in good outcomes in many cases.

Sacral fractures are rare and seldom result in formation of a sacral pseudomeningocele. Treatment of these pseudomeningoceles usually consists of conservative management with flat bedrest or open operative management. The authors describe the case of a 55-year-old woman with an anterior sacral pseudomeningocele that was successfully treated using a lumbar drain for temporary continuous CSF drainage. The patient first presented to an outside institution several days after sacral trauma from an ice skating fall. Initial symptoms included throbbing headaches relieved by lying flat. Head and cervical spine CT demonstrated no abnormality. As symptoms worsened, she presented to another institution where MRI of the lumbar spine indicated sacral fracture with pseudomeningocele. The patient subsequently transferred to the authors' facility, where symptoms included headaches and occasional mild sacral pain. Given her headaches and the authors' concern for CSF leak, another head CT scan was performed. This revealed no subdural hematoma or other abnormality. A subsequent CT myelogram revealed an anterior sacral pseudomeningocele at S3-4 with an anterior irregular linear filling defect, likely representing torn dura. Treatment included placement of a lumbar drain (10 ml/hr) and flat bedrest. Resolution of the CSF leak occurred on postprocedure Day 9. At the 4-week follow-up visit, the patient had no clinical symptoms of CSF leak and no neurological complaints. To our knowledge, this is the first description of temporary continuous CSF drainage used to treat a posttraumatic sacral pseudomeningocele. This technique may reduce the need for potentially complicated surgical repair of sacral fractures associated with CSF leak in select patients.

Object: The objective of this study was to compare the accuracy of 3 methods of ventricular catheter placement during CSF shunt operations: the freehand technique using surface anatomy, ultrasonic guidance, and stereotactic neuronavigation., Methods: This retrospective cohort study included all patients from a single institution who underwent a ventricular CSF shunting procedure in which a new ventricular catheter was placed between January 2005 and March 2010. Data abstracted for each patient included age, sex, diagnosis, method of ventricular catheter placement, site and side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision through December 2011. Statistical analysis was then performed comparing the 3 methods of ventricular catheter placement and to determine risk factors for inaccurate placement., Results: There were 249 patients included in the study; 170 ventricular catheters were freehand passed, 51 were placed using stereotactic neuronavigation, and 28 were placed under intraoperative ultrasonic guidance. There was a statistically significant difference between freehand catheters and stereotactic-guided catheters (p<0.001), as well as between freehand catheters and ultrasound-guided catheters (p<0.001). The only risk factor for inaccurate placement identified in this study was use of the freehand technique. The use of stereotactic neuronavigation and ultrasonic guidance reduced proximal shunt failure rates (p<0.05) in comparison with a freehand technique., Conclusions: Stereotactic- and ultrasound-guided ventricular catheter placements are significantly more accurate than freehand placement, and the use of these intraoperative guidance techniques reduced proximal shunt failure in this study.

Object: The authors conducted a study to review outcomes and management in patients in whom intracranial hemorrhage (ICH) develops during left ventricular assist device (LVAD) therapy., Methods: This retrospective cohort study included all adult patients (18 years of age or older) at a single institution who underwent placement of an LVAD between January 1, 2003, and March 1, 2012. The authors conducted a detailed medical chart review, and data were abstracted to assess outcomes in patients in whom ICH developed compared to those in patients in whom ICH did not develop; to compare management of antiplatelet agents and anticoagulation with outcomes; to describe surgical management employed and outcomes achieved; to compare subtypes of ICH (intraparenchymal, subdural, and subarachnoid hemorrhage) and their outcomes; and to determine any predictors of outcome., Results: During the study period, 330 LVADs were placed and 36 patients developed an ICH (traumatic subarachnoid hemorrhage in 10, traumatic subdural hematoma in 8, spontaneous intraventricular hemorrhage in 1, and spontaneous intraparenchymal hemorrhage in 17). All patients were treated with aspirin and warfarin at the time of presentation. With suspension of these agents, no thromboembolic events or pump failures were seen and no delayed rehemorrhages occurred after resuming these medications. Intraparenchymal hemorrhages had the worst outcomes, with a 30-day mortality rate in 59% compared with a 30-day mortality rate of 0% in patients with traumatic subarachnoid hemorrhages and 13% in those with traumatic subdural hematomas. Five patients with intraparenchymal hemorrhages were managed with surgical intervention, 4 of whom died within 60 days. The only factor found to be predictive of outcome was initial Glasgow Coma Scale score. No patients with a Glasgow Coma Scale score less than 11 survived beyond 30 days. Overall, the development of an ICH significantly reduced survival compared with the natural history of patients on LVAD therapy., Conclusions: The authors' data suggest that withholding aspirin for 1 week and warfarin for 10 days is sufficient to reduce the risk of hemorrhage expansion or rehemorrhage while minimizing the risk of thromboembolic events and pump failure. Patients with intraparenchymal hemorrhage have poor outcomes, whereas patients with traumatic subarachnoid hemorrhage or subdural hematoma have better outcomes.

Object: Arachnoid cysts are a frequent finding on intracranial imaging. The prevalence and natural history of these cysts in adults are not well defined., Methods: We retrospectively reviewed the electronic medical records of a consecutive series of adults who underwent brain MRI over a 12-year interval to identify those with arachnoid cysts. The MRI studies were reviewed to confirm the diagnosis. For those patients with arachnoid cysts, we evaluated presenting symptoms, cyst size, and cyst location. Patients with more than 6 months' clinical and imaging follow-up were included in a natural history analysis., Results: A total of 48,417 patients underwent brain MRI over the study period. Arachnoid cysts were identified in 661 patients (1.4%). Men had a higher prevalence than women (p < 0.0001). Multiple arachnoid cysts occurred in 30 patients. The most common locations were middle fossa (34%), retrocerebellar (33%), and convexity (14%). Middle fossa cysts were predominantly left-sided (70%, p < 0.001). Thirty-five patients were considered symptomatic and 24 underwent surgical treatment. Sellar and suprasellar cysts were more likely to be considered symptomatic (p < 0.0001). Middle fossa cysts were less likely to be considered symptomatic (p = 0.01. The criteria for natural history analysis were met in 203 patients with a total of 213 cysts. After a mean follow-up of 3.8 ± 2.8 years (for this subgroup), 5 cysts (2.3%) increased in size and 2 cysts decreased in size (0.9%). Only 2 patients developed new or worsening symptoms over the follow-up period., Conclusions: Arachnoid cysts are a common incidental finding on intracranial imaging in all age groups. Although arachnoid cysts are symptomatic in a small number of patients, they are associated with a benign natural history for those presenting without symptoms.

Object: This study was undertaken to define the age-related prevalence of cavernous malformations (CMs) in children and young adults undergoing intracranial imaging. In addition, the authors aim to clarify the natural history of CMs in young people, especially in those with incidentally discovered lesions., Methods: To identify those patients with CMs, the authors retrospectively reviewed the electronic medical records of 14,936 consecutive patients 25 years of age or younger who had undergone brain MR imaging. In patients with a CM, clinical and imaging data were collected. Patients with untreated cavernomas who had more than 6 months of clinical and MR imaging follow-up were included in a natural history analysis. The natural history analysis included 110 CMs in 56 patients with a 3.5-year mean clinical follow-up interval (199 patient-years and 361 cavernoma-years)., Results: In 92 patients (0.6%), 164 CMs were identified. The imaging prevalence of cavernomas increased with advancing age (p = 0.002). Multiple CMs occurred in 28 patients (30%), and 8 patients (9%) had a family history of multiple CMs. Fifty patients (54%) presented with symptoms related to the cavernoma, of whom 30 presented with hemorrhage (33%). Of the 164 cavernomas identified, 103 (63%) were considered incidental, asymptomatic lesions. Larger size was associated with acute symptomatic presentation (p = 0.0001). During the follow-up interval, 6 patients with 8 cavernomas developed 11 symptomatic hemorrhages after initial identification. Five of the patients who had a hemorrhage during the follow-up interval had initially presented with hemorrhage, while only 1 had presented incidentally. The hemorrhage rate for all patients in the natural history group was 1.6% per patient-year and 0.9% per cavernoma-year. The hemorrhage rate was 8.0% per patient-year in the symptomatic group versus 0.2% in the incidental group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute presentation (p = 0.02)., Conclusions: The imaging prevalence of CM increases with advancing age during childhood. Patients presenting without hemorrhage have a significantly lower risk of bleeding compared with those who present with acute neurological symptoms. Comparing this series of children to prior analyses of CM natural history in adults, the authors' data do not suggest a higher bleeding risk in younger patients.

Object: We reviewed our experience with pineal cysts to define the natural history and clinical relevance of this common intracranial finding., Methods: The study population consisted of 48,417 consecutive patients who underwent brain MR imaging at a single institution over a 12-year interval and who were over 18 years of age at the time of imaging. Patient characteristics, including demographic data and other intracranial diagnoses, were collected from cases involving patients with a pineal cyst. We then identified all patients with pineal cysts who had been clinically evaluated at our institution and who had at least 6 months of clinical and imaging follow-up. All inclusion criteria for the natural history analysis were met in 151 patients., Results: Pineal cysts measuring 5 mm or larger in greatest dimension were found in 478 patients (1.0%). Of these, 162 patients were male and 316 were female. On follow-up MR imaging of 151 patients with pineal cyst at a mean interval of 3.4 years from the initial study, 124 pineal cysts remained stable, 4 increased in size, and 23 decreased in size. Cysts that were larger at the time of initial diagnosis were more likely to decrease in size over the follow-up interval (p = 0.004). Patient sex, patient age at diagnosis, and the presence of septations within the cyst were not significantly associated with cyst change on follow-up., Conclusions: Follow-up imaging and neurosurgical evaluation are not mandatory for adults with asymptomatic pineal cysts.

Object: The aim of this article was to report on the nature and prevalence of incidental imaging findings in a consecutive series of patients older than 90 years of age who underwent intracranial imaging for any reason., Methods: The authors retrospectively reviewed the electronic medical and imaging records of consecutive patients who underwent brain MR imaging at a single institution over a 153-month interval and were at least 90 but less than 100 years of age at the time of the imaging study. The prevalence of lesions by type in this consecutive series of MR imaging evaluations was calculated for all patients. The authors reviewed the medical record to evaluate whether a change in management was recommended based on MR imaging findings. They evaluated patient age at the time of death and the time interval between MR imaging and death., Results: The authors identified 177 patients who met the study criteria. The group included 119 women (67%) and 58 (33%) men. Their mean age was 92.3 ± 1.8 years. Evidence of acute ischemic changes or cerebrovascular accident (CVA) was found in 36 patients (20%). Fifteen patients (8%) had an intracranial tumor. Intracranial aneurysms were incidentally identified in 6 patients (3%). Chronic subdural hematomas were found in 3 patients (2%). Overall, 25 patients (14%) had some change in medical management as a result of the MR imaging findings. The most common MR imaging finding that resulted in a change in medical management was an acute CVA (p < 0.0001). The mean time to death from date of MR imaging was 2.5 ± 2.3 years., Conclusions: Intracranial imaging is rarely performed in patients older than 90 years. In cases of suspected stroke, MR imaging findings may influence treatment decisions. Brain MR imaging studies ordered for other indications in this age group rarely influence treatment decisions. Incidentally discovered lesions in this age group are generally not treated.

Intrathecal liposomal cytarabine (ITLC) has shown prolonged time to neurological deterioration in some patients with leptomeningeal spread of breast cancer. We describe a patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. A 56-year-old Caucasian female developed progressive headache, depressed level of consciousness and adventitious movements immediately following ITLC. Neurological examination was normal prior to injection. This progressed to loss of all brainstem function and a head CT scan demonstrated diffuse cerebral edema. Due to the absence of neurological function on examination, the family opted to withdraw care. To our knowledge we report the first patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. Adjunctive glucocorticoids are recommended. Treatment options are limited and complicated by the liposomal formulation of intrathecal cytarabine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Arteriovenous malformations (AVMs) are the most frequently encountered structural cause of spontaneous intracerebral hemorrhage in childhood, excluding hemorrhages of prematurity. The goal of our study was to examine the relationship between age and AVM prevalence on imaging in children, which to date has not been well described., Methods: We queried the electronic and radiographic records of 14,936 consecutive patients aged 25 years or less who had undergone brain magnetic resonance imaging (MRI) at a single institution over an 11-year period to identify those with a cerebral AVM. We collected age, gender, and other demographic characteristics for all patients. For all patients with a cerebral AVM, we recorded the location, size, drainage pattern, Spetzler-Martin grade, medical history, and presence of neurological symptoms., Results: Cerebral AVMs were identified in 55 patients (0.37%). The prevalence of AVMs detected on MRI significantly increased with age (p = 0.001). AVMs were found in 0.34% of boys (25 of 7,447) and 0.40% of girls (30 of 7,489). AVMs were most commonly identified in the frontal lobes (36%), followed by parietal (20%) and temporal lobes (13%). Sixty percent (n = 33) of AVMs were less than 3 cm in size, 35% (n = 19) were 3-6 cm in size, and 5.5% (n = 3) were greater than 6 cm in size. As for Spetzler-Martin grade of the AVMs, 25.5% were grade I, 18.2% were grade II, 36.4% were grade III, 16.4% were grade IV, and 3.6% were grade V., Conclusions: AVMs are seen more frequently on MRI with advancing age in children and young adults.

Object: Arachnoid cysts are a frequent finding on intracranial imaging in children. The prevalence and natural history of these cysts are not well defined. The authors studied a large consecutive series of children undergoing MR imaging to better define both the MR imaging-demonstrated prevalence and behavior of these lesions over time., Methods: The authors reviewed a consecutive series of 11,738 patients who were 18 years of age or younger and had undergone brain MR imaging at a single institution during an 11-year period. In the patients in whom intracranial arachnoid cysts were identified, clinical and demographic information was recorded and imaging characteristics, such as cyst size and location, were evaluated. Prevalence data were analyzed using univariate and multivariate logistic regression, linear regression, and ANOVA. All patients with sufficient data (repeat MR imaging studies as well as repeated clinical evaluation over at least 5 months) for a natural history analysis were identified. This group was assessed for any change in symptoms or imaging appearance during the follow-up interval., Results: Three hundred nine arachnoid cysts (2.6% prevalence rate) were identified. There was an increased prevalence of arachnoid cysts in males (p < 0.000001). One hundred eleven patients met all criteria for inclusion in the natural history analysis. After a mean follow-up of 3.5 years, 11 arachnoid cysts increased in size, 13 decreased, and 87 remained stable. A younger age at presentation was significantly associated with cyst enlargement (p = 0.001) and the need for surgery (p = 0.05). No patient older than 4 years of age at the time of initial diagnosis had cyst enlargement, demonstrated new symptoms, or underwent surgical treatment., Conclusions: Arachnoid cysts are a common incidental finding on intracranial imaging in pediatric patients. An older age at the time of presentation is associated with a lack of clinical or imaging changes over time.

The trans-oral approach allows direct access to pathologies of the anterior craniocervical junction. However, the classic midline incision of the posterior pharyngeal wall can be surgically burdensome and limits lateral exposure. We reviewed the medical records of nine patients undergoing the trans-oral approach. The sites of the pathology ranged from the clivus to C2, and surgical exposure ranged from the clivus to C3. Each operation utilized an inferiorly based flap. None of the patients experienced vascular or neurologic complications, and no patient had a cerebrospinal fluid fistula, pseudomeningocele, or meningitis postoperatively. The trans-oral approach with an inferiorly based flap can therefore be safely and effectively performed with minimal oropharyngeal and neurologic morbidity. Not only does a U-shaped flap allow adequate exposure from the lower half of the clivus to C3, a flap improves lateral exposure, provides a clear operating field, and allows superficial mucosal closure not directly overlying the operative field., ((c) 2009 Elsevier Ltd. All rights reserved.)

Object: The authors reviewed their experience with pediatric pineal cysts to define the natural history and clinical relevance of this common intracranial finding., Methods: The authors identified all patients with pineal cysts who had been clinically evaluated at their institution over an 11.5-year interval and were < 25 years of age at the time of diagnosis. All inclusion criteria were met in 106 patients, and included repeated MR imaging as well as repeated clinical evaluation over at least a 6-month interval., Results: The mean age at diagnosis was 11.7 +/- 7.2 years. Forty-two patients were male and 64 were female. On follow-up MR imaging evaluation at a mean interval of 3.0 years from the initial study, 98 pineal cysts had no increase in size and no change in imaging appearance. Six pineal cysts increased in size and 2 others had a change in imaging characteristics without associated growth. Younger age was associated with cyst change or growth on follow-up imaging (p = 0.02). The mean age of patients with cysts that changed or grew was 5.5 years, and the mean age of patients with stable pineal cysts was 12.2 years. Initial cyst size and appearance on MR imaging were not significant predictors of growth or change in imaging appearance at follow-up. Similarly, the patient's sex was not a significant predictor of growth or change in imaging characteristics., Conclusions: Follow-up imaging and neurosurgical evaluation may be considered optional in older children with pineal cysts.

Background: Although most patients with an implanted ventriculoperitoneal shunt device will require cerebrospinal fluid diversion over the course of their lifetime, there appears to be a small number of patients that are shunt independent and may benefit from shunt removal., Methods: We retrospectively analyzed 661 patients with hydrocephalus treated over a 10-year period at a single institution. In 10 patients, a systematic shunt weaning protocol was attempted before removal of the cerebrospinal fluid shunt., Results: Ten patients underwent an attempt at shunt removal. Seven of these patients were successfully weaned and 3 were not. The indications to attempt shunt removal for the 7 patients that were successfully weaned were recurrent complications and infections requiring multiple shunt externalizations and revisions in 4 patients, asymptomatic shunt disconnection in 2 patients, and symptomatic overdrainage in 1 patient. None of the patients that were successfully weaned had a history of shunt failure resulting in ventriculomegaly. Two of the 3 patients who failed shunt weaning attempts had a history of shunt failure that resulted in ventriculomegaly., Conclusion: A small number of patients with shunted hydrocephalus may benefit from removal of their shunt., (Copyright © 2010 S. Karger AG, Basel.)

Object: Pineal cysts are a frequent incidental finding on intracranial imaging. In adults, the prevalence of pineal cysts is estimated to be 1.1-4.3%. However, the prevalence is not well established in younger patients., Methods: The authors retrospectively reviewed a consecutive series of 14,516 patients 25 years of age and younger, who underwent brain MR imaging at a single institution over an 11-year period. In patients identified with pineal cysts, the authors analyzed the images according to cyst size, signal characteristics, enhancement pattern, and evidence of local mass effect. Patient characteristics including demographics and other intracranial diagnoses were collected in the pineal cyst population and compared with a randomly selected age- and sex-matched control patient population. The data were evaluated using univariate and multivariate logistic regression, linear regression, and ANOVA., Results: The authors identified 288 pineal region cysts (2.0%). The prevalence of pineal cysts was higher in female (2.4%) than in male patients (1.5%; p < 0.001). Pineal cysts were identified in patients of all ages, with an increased prevalence found in older patients (p < 0.001). Pineal cyst size was similar for all age and sex groups., Conclusions: Pineal cysts are common in the pediatric population, with an increased prevalence in girls and in older patients.

Object: After primary repair of a myelomeningocele or a lipomyelomeningocele, patients can present with symptoms of secondary tethered cord syndrome (TCS). After surgical untethering, a small percentage of these patients can present with multiple repeat TCS. In patients presenting with secondary or multiple repeat TCS, the role as well the expected outcomes of surgical untethering are not well defined., Methods: Eighty-four patients who underwent spinal cord untethering after at least 1 primary repair were retrospectively evaluated using scaled and subjective outcome measures at short-term and long-term follow-up visits. Outcomes were analyzed for predictive measures using multivariate logistic regression., Results: Surgical untethering was performed in 66 patients with myelomeningoceles and 18 patients with lipomyelomeningoceles. Fourteen patients underwent multiple repeat spinal cord untethering. Patients were followed up for an average of 6.2 years. Most patients had stability of function postoperatively. Motor function and weakness improved in 7 and 16% of patients at 6 months, respectively, and 6 and 19% of patients at long-term follow-up evaluation, respectively. Of the patients who presented with back pain, 75% had improvement in symptoms at 6 months postoperatively. Younger age at untethering was significantly associated with worse long-term neurological outcomes. The number of previous untethering procedures, original diagnosis, sex, anatomical level, and degree of untethering had no effect on surgical outcomes., Conclusions: Patients presenting with secondary or multiple repeat TCS may benefit from surgical untethering.

Our current understanding of nonaccidental head injury in children is the result of decades of effort and the tireless work of numerous physicians. In 1860 Auguste Ambroise Tardieu, a French forensics expert, recognized important patterns of injury in children and identified nonaccidental trauma as the cause of these injuries. His work was ignored. In the years that followed, physicians continued to report these patterns of injury but were unable to identify the etiology. A fundamental misunderstanding of the usual cause of subdural hematoma (SDH) contributed to the confusion at that time. Early in the 20th century, neurosurgeons such as Wilfred Trotter recognized that SDHs were traumatic in origin. However, even Trotter's efforts to expose faults in the theories that SDHs primarily resulted from inflammatory or infectious processes were not accepted immediately. Eventually, the pattern of injuries in children was again recognized both by neurosurgeons, who began to identify an association between trauma-induced SDHs and retinal hemorrhages, and by radiologists, who began to note SDHs in conjunction with osseous lesions. Not until the 1950s and 1960s, however, did physicians begin to routinely identify nonaccidental trauma as the cause of these injuries. Following the recognition of child abuse, a pattern of injuries in conjunction with shaking was identified and is currently known as shaken baby syndrome. Since its identification, our understanding of this syndrome has been modified as a result of new medical research, legal challenges, and popular media forces.

Myelomeningocele is associated with other neurological abnormalities, including hydrocephalus, Chiari II malformations, syringomyelia, and secondary tethered cord syndrome. Tethered cord syndrome occurs because of abnormal attachment of the spinal cord to the caudal dural sac, causing cord ischemia. Occasionally, symptoms of progressive neurological deterioration may occur and can significantly affect the long-term outcome of these patients. Proper management of patients with myelomeningocele requires long-term follow-up and evaluation of signs of neurological deterioration that suggest secondary tethered cord syndrome. Treatment of these patients may target symptoms, such as urological intervention for bladder dysfunction, or it may target the tethered cord itself. Recently, many studies have shown that tethered cord release can significantly improve symptoms in these patients.

Primary traumatic facet dislocations are unusual in the lumbar spine. Most occurrences have been reported at the lumbosacral junction associated with anterior subluxation. The authors describe 2 cases in which a high impact trauma resulted in lateral subluxation with a unilateral locked facet involving the lumbar spine. In their review of the literature, the authors found no previously reported cases of this type of injury. Both cases described in this report involved significant spinal stenosis, neurological injury, and spinal instability. A posterior surgical approach, with at least partial resection of the locked facet joint in conjunction with pedicle screw fixation, allowed successful reduction and stabilization of the injury.

Introduction: It is unclear how to manage high risk hemodialysis patients who present with an indwelling catheter. The National Kidney Foundation Practice Guidelines urge prompt removal of the catheter, but the guidelines do not specifically address the problem of patients whose only option is a femoral arteriovenous (AV) graft., Methods: This study was a retrospective review of all patients who underwent femoral AV graft placement for hemodialysis access between January 1, 1996 and January 1, 2003 at the University of Michigan Health System (UMHS). Graft patency is reported according to the standards developed by the Society of Vascular Surgery and the American Association of Vascular Surgeons., Results: Thirty patients were identified who had undergone femoral AV graft placement. The mean follow-up was 23 months (range 1-75 months). The patients had had significant medical co-morbidities and multiple previous access operations (mean 3; interquartile range 1-5). The 1-year secondary graft patency rate was 41%, the 2-year rate was 26%, and the 3-year rate was 21%. Infection was the cause of final graft loss in eight patients (50% of the grafts losses, 27% of the total grafts placed.) Among those who died (n=14), the mean time from femoral graft placement to death was 31.2+/-27.5 months. The patient survival was quite low: at 1 year 81%, at 2 years 68%, and at 3 years 54%., Conclusions: These complex patients who have exhausted their upper extremity hemodialysis options do poorly following femoral AV graft placement. Consideration should be given to long-term catheter-based access in some of these patients.