Search

Evaluation of intracranial artery morphology plays an important role in diagnosing a variety of neurovascular diseases. In addition to clinical symptoms, diagnosis currently relies on qualitative rather than quantitative evaluation of vascular imaging sequences, such as magnetic resonance angiography (MRA). However, there is a paucity of literature on normal arterial morphology in the pediatric population across brain development. We aimed to quantitatively assess normal, age-related changes in artery morphology in children. We performed retrospective analysis of pediatric MRA data obtained from a tertiary referral center. An MRA dataset from 98 children (49 boys/49 girls) aged 0.6–20 years (median = 11.5 years) with normal intracranial vasculature was retrospectively collected between 2011 and 2018. All arteries were automatically segmented to determine the vessel radius. Using an atlas-based approach, the average radius and density of arteries were measured in the three main cerebral vascular territories and the radius of five major arteries was determined at corresponding locations. The radii of the major arteries as well as the average artery radius and density in the different vascular territories in the brain remained constant throughout childhood and adolescence (|r

OBJECTIVECavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.METHODSPediatric patients (≤ 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher’s exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.RESULTSFifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).CONCLUSIONSPatients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.

OBJECTIVETransnasal endoscopic transsphenoidal approaches constitute an essential technique for the resection of skull base tumors in adults. However, in the pediatric population, sellar and suprasellar lesions have historically been treated by craniotomy. Transnasal endoscopic approaches are less invasive and thus may be preferable to craniotomy, especially in children. In this case series, the authors present their institutional experience with transnasal endoscopic transsphenoidal approaches for pediatric skull base tumors.METHODSThe authors retrospectively reviewed pediatric patients (age ≤ 18 years) who had undergone transnasal endoscopic transsphenoidal approaches for either biopsy or resection of sellar or suprasellar lesions between 2007 and 2016. All operations were performed jointly by a team of pediatric neurosurgeons and skull base otolaryngologists, except for 8 cases performed by one neurosurgeon.RESULTSThe series included 42 patients between 4 and 18 years old (average 12.5 years) who underwent 51 operations. Headache (45%), visual symptoms (69%), and symptoms related to hormonal abnormalities (71%) were the predominant presenting symptoms. Improvement in preoperative symptoms was seen in 92% of cases. Most patients had craniopharyngiomas (n = 16), followed by pituitary adenomas (n = 12), Rathke cleft cysts (n = 4), germinomas (n = 4), chordomas (n = 2), and other lesion subtypes (n = 4). Lesions ranged from 0.3 to 6.2 cm (median 2.5 cm) in their greatest dimension. Gross-total resection was primarily performed (63% of cases), with 5 subsequent recurrences. Nasoseptal flaps were used in 47% of cases, fat grafts in 37%, and lumbar drains in 47%. CSF space was entered intraoperatively in 15 cases, and postoperative CSF was observed only in lesions with suprasellar extension. There were 8 cases of new hormonal deficits and 3 cases of new cranial nerve deficits. Length of hospital stay ranged from 1 to 61 days (median 5 days). Patients were clinically followed up for a median of 46 months (range 1–120 months), accompanied by a median radiological follow-up period of 45 months (range 3.8–120 months). Most patients (76%) were offered adjuvant therapy.CONCLUSIONSIn this single-institution report of the transnasal endoscopic transsphenoidal approach, the authors demonstrated that this technique is generally safe and effective for different types of pediatric skull base lesions. Favorable effects of surgery were sustained during a follow-up period of 4 years. Further refinement in technology will allow for more widespread use in the pediatric population.

BACKGROUND Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes. OBJECTIVE To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage. METHODS We retrospectively reviewed children (

Evaluation of intracranial artery morphology plays an important role in diagnosing a variety of neurovascular diseases. In addition to clinical symptoms, diagnosis currently relies on qualitative rather than quantitative evaluation of vascular imaging sequences, such as magnetic resonance angiography (MRA). However, there is a paucity of literature on normal arterial morphology in the pediatric population across brain development. We aimed to quantitatively assess normal, age-related changes in artery morphology in children.We performed retrospective analysis of pediatric MRA data obtained from a tertiary referral center. An MRA dataset from 98 children (49 boys/49 girls) aged 0.6-20 years (median = 11.5 years) with normal intracranial vasculature was retrospectively collected between 2011 and 2018. All arteries were automatically segmented to determine the vessel radius. Using an atlas-based approach, the average radius and density of arteries were measured in the three main cerebral vascular territories and the radius of five major arteries was determined at corresponding locations.The radii of the major arteries as well as the average artery radius and density in the different vascular territories in the brain remained constant throughout childhood and adolescence (|r| 0.369 in all cases).This study presents the first automated evaluation of intracranial vessel morphology on MRA across childhood. Our results can serve as a framework for quantitative evaluation of cerebral vessel morphology in the setting of pediatric neurovascular diseases.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system (CNS) tumor diagnosed primarily in infants and usually portends a poor prognosis. Despite being the most common embryonal tumor in children less than 1 year old, diagnosis is difficult to make based on clinical findings or imaging alone. A complete diagnosis of AT/RT requires identification of loss of integrase interactor 1 (INI1) protein or the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) gene, in its most common presentation. Moreover, their presentation with other primary rhabdoid tumors in the body raises significant suspicion for rhabdoid tumor predisposition syndrome (RTPS). We report a case of a one-month-old infant admitted for worsening emesis and failure to thrive, who was later found to have brain and bladder masses on radiologic imaging. Autopsy with subsequent immunoprofile and molecular testing were crucial in establishing the absence of INI1 nuclear expression and possible homozygous deletion of SMARCB1 in the urinary bladder tumor tissue. Sequencing of the peripheral blood demonstrated probable single copy loss at the SMARCB1 locus. The constellation of findings in tumor and peripheral blood sequencing suggested the possibility of germline single copy SMARCB1 loss, followed by somatic loss of the remaining SMARCB1 allele due to copy neutral loss-of-heterozygosity. Such a sequence of genetic events has been described in malignant rhabdoid tumors (MRT). Dedicated germline testing of this patient’s family members could yield answers as to whether rhabdoid tumor predisposition syndrome will continue to have implications for the patient’s family.

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

BACKGROUND AND PURPOSE: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging–based deep learning model for posterior fossa tumor detection and tumor pathology classification. MATERIALS AND METHODS: The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists. RESULTS: Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists. CONCLUSIONS: We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.

OBJECTIVEImaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals.METHODSThe study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as “ground truth” data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software.RESULTSModel segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan).CONCLUSIONSThe authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.

OBJECTIVEPediatric spinal astrocytomas are rare spinal lesions that pose unique management challenges. Therapeutic options include gross-total resection (GTR), subtotal resection (STR), and adjuvant chemotherapy or radiation therapy. With no randomized controlled trials, the optimal management approach for children with spinal astrocytomas remains unclear. The aim of this study was to conduct a systematic review and meta-analysis on pediatric spinal astrocytomas.METHODSThe authors performed a systematic review of the PubMed/MEDLINE electronic database to investigate the impact of histological grade and extent of resection on overall survival among patients with spinal cord astrocytomas. They retained publications in which the majority of reported cases included astrocytoma histology.RESULTSTwenty-nine previously published studies met the eligibility criteria, totaling 578 patients with spinal cord astrocytomas. The spinal level of intramedullary spinal cord tumors was predominantly cervical (53.8%), followed by thoracic (40.8%). Overall, resection was more common than biopsy, and GTR was slightly more commonly achieved than STR (39.7% vs 37.0%). The reported rates of GTR and STR rose markedly from 1984 to 2015. Patients with high-grade astrocytomas had markedly worse 5-year overall survival than patients with low-grade tumors. Patients receiving GTR may have better 5-year overall survival than those receiving STR.CONCLUSIONSThe authors describe trends in the management of pediatric spinal cord astrocytomas and suggest a benefit of GTR over STR for 5-year overall survival.

Objective The need for neurosurgical supervision as well as the general safety and utility of dynamic magnetic resonance imaging (MRI) of the cervical spine in children remains controversial. We present the largest descriptive cohort study of cervical flexion-extension MRI scans in pediatric patients to help elucidate the safety and utility of this technique. Methods We retrospectively reviewed all cervical spine MRI scans performed at Lucile Packard Children's Hospital at Stanford from 2009 to 2015. We identified 66 dynamic cervical MRI scans performed in 45 children and 2 young adults for further study. Results General anesthesia was used in 43 scans. The neuroradiology team performed all scans with no direct supervision by the neurosurgery team. There were no adverse events. Dynamic MRI detected significant instability that was not clearly seen on dynamic radiographs (5 patients) and cord compression not seen on static MRI (9 patients). One patient with asymptomatic instability found on flexion-extension radiographs had no cord compression with movement on MRI and was managed conservatively. Two neonates with significant congenital malformations of the cervical spine were cleared for operative positioning for cardiac procedures based on flexion-extension MRI. Conclusions Dynamic MRI is a safe tool for evaluating the cervical spine and cervicomedullary junction in various pediatric populations and can be performed safely without direct neurosurgical supervision. We describe for the first time the use of flexion-extension MRI to clear neonates with severe congenital cervical spine abnormalities for complex operative positioning and further care in the intensive care unit.

Background Spontaneous intrauterine depressed skull fractures (IDSFs) are rare fractures that often require neurosurgical evaluation and therapy. Most of the reported congenital depressions are secondary to maternal abdominal trauma or instrumentation during delivery. Spontaneous IDSFs occur in the setting of uneventful normal spontaneous vaginal delivery or cesarean section, without obvious predisposing risk factors. The etiology and optimal management of spontaneous IDSFs remain controversial. Case Description We describe 2 cases of spontaneous IDSF who underwent cranioplasty at our institution using an absorbable mesh, as well as review the current state of knowledge regarding the diagnosis and management of spontaneous IDSF. The 2 neonates, 1 male and 1 female, presented at Lucile Packard Children's Hospital with spontaneous IDSF after uneventful normal spontaneous vaginal deliveries. The fractures were located in the left frontal and right parietotemporal calvarium, respectively. Both patients underwent open craniotomy and elevation of their IDSFs with mesh cranioplasty. At last follow-up, both patients were normocephalic and neurologically intact. Conclusions Neurosurgery consultation is necessary for initial evaluation of spontaneous IDSF. Surgical intervention is indicated for larger defects and/or intracranial involvement. Expectant management and negative-pressure elevation have also been shown to be effective.

Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recently, endoscopic transsphenoidal approaches have been increasingly used; however, few case series exist in the pediatric population.A retrospective review of patients (aged18 years) undergoing endoscopic transsphenoidal resection of craniopharyngiomas between 1995 and 2016 was performed. Preoperative data included presenting symptoms, tumor size, location, and components. Postoperative outcomes included symptom resolution, visual outcomes, endocrine outcomes, disease recurrence, and major complications.Sixteen pediatric patients with mean age of 11.0 years (range, 5-15 years) were included. The median follow-up time was 56.2 months. Mean maximal tumor diameter was 3.98 cm. Most of the tumors had suprasellar (93.8%) and intrasellar (68.8%) components. The gross total resection rate was 93.8%. The most common presenting symptoms were vision changes (81.3%) and increased intracranial pressure (56.3%). Most patients (66.7%) had their presenting symptoms resolved by their first postoperative visit. Vision improved or remained normal in 69.2% of patients. Postoperatively, new incidence of panhypopituitarism or diabetes insipidus developed in 63.6% and 46.7% of patients, respectively. New hypothalamic obesity developed in 28.6% of patients. The postoperative cerebrospinal fluid leak rate was 18.8%. One patient died of intraventricular hemorrhage postoperatively. The major complication rate was 12.5%. Disease recurrence occurred in 1 patient with gross total resection (6.3%).Endoscopic transsphenoidal resection for craniopharyngiomas can achieve high rates of total resection with low rates of disease recurrence in larger tumors than previously described. However, hypothalamic-pituitary dysfunction and cerebrospinal fluid leak remain significant postoperative morbidities.

Parapharyngeal infection is the most common deep neck space infection in children and, in rare instances, can result in bony destruction of the cervical spine. We report one such case that required occipital to cervical fusion and halo-vest fixation. We also review the literature and discuss the etiology, diagnosis, and treatment options for managing pediatric cervical bony destruction secondary to infection.

BACKGROUND Brain tumors are the most common solid malignancies in childhood, many of which develop in the posterior fossa (PF). Manual tumor measurements are frequently required to optimize registration into surgical navigation systems or for surveillance of nonresectable tumors after therapy. With recent advances in artificial intelligence (AI), automated MRI-based tumor segmentation is now feasible without requiring manual measurements. Our goal was to create a deep learning model for automated PF tumor segmentation that can register into navigation systems and provide volume output. METHODS 720 pre-surgical MRI scans from five pediatric centers were divided into training, validation, and testing datasets. The study cohort comprised of four PF tumor types: medulloblastoma, diffuse midline glioma, ependymoma, and brainstem or cerebellar pilocytic astrocytoma. Manual segmentation of the tumors by an attending neuroradiologist served as “ground truth” labels for model training and evaluation. We used 2D Unet, an encoder-decoder convolutional neural network architecture, with a pre-trained ResNet50 encoder. We assessed ventricle segmentation accuracy on a held-out test set using Dice similarity coefficient (0–1) and compared ventricular volume calculation between manual and model-derived segmentations using linear regression. RESULTS Compared to the ground truth expert human segmentation, overall Dice score for model performance accuracy was 0.83 for automatic delineation of the 4 tumor types. CONCLUSIONS In this multi-institutional study, we present a deep learning algorithm that automatically delineates PF tumors and outputs volumetric information. Our results demonstrate applied AI that is clinically applicable, potentially augmenting radiologists, neuro-oncologists, and neurosurgeons for tumor evaluation, surveillance, and surgical planning.

OBJECTIVESpine MRI is a diagnostic modality for evaluating pediatric CNS tumors. Applying diffusion-weighted MRI (DWI) or diffusion tensor imaging (DTI) to the spine poses challenges due to intrinsic spinal anatomy that exacerbates various image-related artifacts, such as signal dropouts or pileups, geometrical distortions, and incomplete fat suppression. The zonal oblique multislice (ZOOM)–echo-planar imaging (EPI) technique reduces geometric distortion and image blurring by reducing the field of view (FOV) without signal aliasing into the FOV. The authors hypothesized that the ZOOM-EPI method for spine DTI in concert with conventional spinal MRI is an efficient method for augmenting the evaluation of pediatric spinal tumors.METHODSThirty-eight consecutive patients (mean age 8 years) who underwent ZOOM-EPI spine DTI for CNS tumor workup were retrospectively identified. Patients underwent conventional spine MRI and ZOOM-EPI DTI spine MRI. Two blinded radiologists independently reviewed two sets of randomized images: conventional spine MRI without ZOOM-EPI DTI, and conventional spine MRI with ZOOM-EPI DTI. For both image sets, the reviewers scored the findings based on lesion conspicuity and diagnostic confidence using a 5-point Likert scale. The reviewers also recorded presence of tumors. Quantitative apparent diffusion coefficient (ADC) measurements of various spinal tumors were extracted. Tractography was performed in a subset of patients undergoing presurgical evaluation.RESULTSSixteen patients demonstrated spinal tumor lesions. The readers were in moderate agreement (kappa = 0.61, 95% CI 0.30–0.91). The mean scores for conventional MRI and combined conventional MRI and DTI were as follows, respectively: 3.0 and 4.0 for lesion conspicuity (p = 0.0039), and 2.8 and 3.9 for diagnostic confidence (p < 0.001). ZOOM-EPI DTI identified new lesions in 3 patients. In 3 patients, tractography used for neurosurgical planning showed characteristic fiber tract projections. The mean weighted ADCs of low- and high-grade tumors were 1201 × 10−6 and 865 × 10−6 mm2/sec (p = 0.002), respectively; the mean minimum weighted ADCs were 823 × 10−6 and 474 × 10−6 mm2/sec (p = 0.0003), respectively.CONCLUSIONSDiffusion MRI with ZOOM-EPI can improve the detection of spinal lesions while providing quantitative diffusion information that helps distinguish low- from high-grade tumors. By adding a 2-minute DTI scan, quantitative diffusion information and tract profiles can reliably be obtained and serve as a useful adjunct to presurgical planning for pediatric spinal tumors.

OBJECTIVEPosterior fossa syndrome (PFS) is a common postoperative complication following resection of posterior fossa tumors in children. It typically presents 1 to 2 days after surgery with mutism, ataxia, emotional lability, and other behavioral symptoms. Recent structural MRI studies have found an association between PFS and hypertrophic olivary degeneration, which is detectable as T2 hyperintensity in the inferior olivary nuclei (IONs) months after surgery. In this study, the authors investigated whether immediate postoperative diffusion tensor imaging (DTI) of the ION can serve as an early imaging marker of PFS.METHODSThe authors retrospectively reviewed pediatric brain tumor patients treated at their institution, Lucile Packard Children’s Hospital at Stanford, from 2004 to 2016. They compared the immediate postoperative DTI studies obtained in 6 medulloblastoma patients who developed PFS to those of 6 age-matched controls.RESULTSPatients with PFS had statistically significant increased mean diffusivity (MD) in the left ION (1085.17 ± 215.51 vs 860.17 ± 102.64, p = 0.044) and variably increased MD in the right ION (923.17 ± 119.2 vs 873.67 ± 60.16, p = 0.385) compared with age-matched controls. Patients with PFS had downward trending fractional anisotropy (FA) in both the left (0.28 ± 0.06 vs 0.23 ± 0.03, p = 0.085) and right (0.29 ± 0.06 vs 0.25 ± 0.02, p = 0.164) IONs compared with age-matched controls, although neither of these values reached statistical significance.CONCLUSIONSIncreased MD in the ION is associated with development of PFS. ION MD changes may represent an early imaging marker of PFS.

OBJECTIVEChildren with intracranial arteriovenous malformations (AVMs) undergo digital DSA for lesion surveillance following their initial diagnosis. However, DSA carries risks of radiation exposure, particularly for the growing pediatric brain and over lifetime. The authors evaluated whether MRI enhanced with a blood pool ferumoxytol (Fe) contrast agent (Fe-MRI) can be used for surveillance of residual or recurrent AVMs.METHODSA retrospective cohort was assembled of children with an established AVM diagnosis who underwent surveillance by both DSA and 3-T Fe-MRI from 2014 to 2016. Two neuroradiologists blinded to the DSA results independently assessed Fe-enhanced T1-weighted spoiled gradient recalled acquisition in steady state (Fe-SPGR) scans and, if available, arterial spin labeling (ASL) perfusion scans for residual or recurrent AVMs. Diagnostic confidence was examined using a Likert scale. Sensitivity, specificity, and intermodality reliability were determined using DSA studies as the gold standard. Radiation exposure related to DSA was calculated as total dose area product (TDAP) and effective dose.RESULTSFifteen patients were included in this study (mean age 10 years, range 3–15 years). The mean time between the first surveillance DSA and Fe-MRI studies was 17 days (SD 47). Intermodality agreement was excellent between Fe-SPGR and DSA (κ = 1.00) but poor between ASL and DSA (κ = 0.53; 95% CI 0.18–0.89). The sensitivity and specificity for detecting residual AVMs using Fe-SPGR were 100% and 100%, and using ASL they were 72% and 100%, respectively. Radiologists reported overall high diagnostic confidence using Fe-SPGR. On average, patients received two surveillance DSA studies over the study period, which on average equated to a TDAP of 117.2 Gy×cm2 (95% CI 77.2–157.4 Gy×cm2) and an effective dose of 7.8 mSv (95% CI 4.4–8.8 mSv).CONCLUSIONSFe-MRI performed similarly to DSA for the surveillance of residual AVMs. Future multicenter studies could further investigate the efficacy of Fe-MRI as a noninvasive alternative to DSA for monitoring AVMs in children.

The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.

Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through the activation of TWIST1. NOTCH1 expression and activity are directly related to medulloblastoma metastasis and decreased survival rate of tumor-bearing mice. Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3 medulloblastoma metastasis and self-renewal, supporting the development of therapies targeting this pathway., Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.

OBJECTIVEPosterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated; however, the wide-ranging symptoms of PFS suggest the possibility of widespread cortical dysfunction. In this study, the authors utilized arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS.METHODSA database of medulloblastoma treated at the authors’ institution from 2004 to 2016 was retrospectively reviewed, and 14 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL.RESULTSOn immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend toward decreased perfusion in the left frontal lobe compared with controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared with their immediate postoperative imaging findings.CONCLUSIONSASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiological correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiological explanation for the transient symptoms of PFS.

Background Current standard of care for children with infratentorial ependymoma includes maximal safe resection and local radiation of 54−59 Gray. High-dose local radiation has been associated with declines in multiple cognitive domains. The anatomic and physiologic correlates of this cognitive decline remain undefined, and there have been no radiographic studies on the long-term effects of this treatment paradigm. Methods A comprehensive database of pediatric brain tumor patients treated at Stanford Children's from 2004−2016 was queried. Seven patients with posterior fossa ependymoma who were treated with surgery and local radiation alone, who had no evidence of recurrent disease, and had imaging suitable for analysis were identified. Diffusion-weighted magnetic resonance imaging datasets were used to calculate apparent diffusion coefficient maps for each subject, while arterial spin labeling datasets were used to calculate maps of cerebral blood flow. Diffusion-weighted imaging and arterial spin labeling datasets of 52 age-matched healthy children were analyzed in the same fashion to enable group comparisons. Results Several statistically significant differences were detected between the 2 groups. Cerebral blood flow was lower in the caudate and pallidum and higher in the nucleus accumbens in the ependymoma cohort compared with controls. Apparent diffusion coefficient was increased in the thalamus and trended toward decreased in the amygdala. Conclusions Surgery and local radiation for posterior fossa ependymoma are associated with supratentorial apparent diffusion coefficient and cerebral blood flow alterations, which may represent an anatomic and physiologic correlate to the previously published decline in neurocognitive outcomes in this population.

INTRODUCTION: Posterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated, however the wide-ranging symptoms of PFS suggest the possibility of wide-spread cortical dysfunction. In this study, we utilize arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS. METHODS: A database of pediatric brain tumor patients treated at Stanford from 2004-2016 was retrospectively reviewed and 15 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and age-matched medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL. RESULTS: On immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend towards decreased perfusion in the left frontal lobe compared to controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared to their immediate postoperative imaging. CONCLUSION: ASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiologic correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiologic explanation for the transient symptoms of PFS.

OBJECTIVEFast magnetic resonance imaging (fsMRI) sequences are single-shot spin echo images with fast acquisition times that have replaced CT scans for many conditions. Introduced as a means of evaluating children with hydrocephalus and macrocephaly, these sequences reduce the need for anesthesia and can be more cost-effective, especially for children who require multiple surveillance scans. However, the role of fsMRI has yet to be investigated in evaluating the posterior fossa in patients with Chiari I abnormality (CM-I). The goal of this study was to examine the diagnostic performance of fsMRI in evaluating the cerebellar tonsils in comparison to conventional MRI.METHODSThe authors performed a retrospective analysis of 18 pediatric patients with a confirmed diagnosis of CM-I based on gold-standard conventional brain MRI and 30 controls without CM-I who had presented with various neurosurgical conditions. The CM-I patients were included if fsMRI studies had been obtained within 1 year of conventional MRI with no surgical intervention between the studies. Two neuroradiologists reviewed the studies in a blinded fashion to determine the diagnostic performance of fsMRI in detecting CM-I. For the CM-I cohort, the fsMRI and T2-weighted MRI exams were randomized, and the blinded reviewers performed tonsillar measurements on both scans.RESULTSThe mean age of the CM-I cohort was 7.39 years, and 50% of these subjects were male. The mean time interval between fsMRI and conventional T2-weighted MRI was 97.8 days. Forty-four percent of the subjects had undergone imaging after posterior fossa decompression. The sensitivity and specificity of fsMRI in detecting CM-I was 100% (95% CI 71.51%–100%) and 92.11% (95% CI 78.62%–98.34%), respectively. If only preoperative patients are considered, both sensitivity and specificity increase to 100%. The authors also performed a cost analysis and determined that fsMRI was significantly cost-effective compared to T2-weighted MRI or CT.CONCLUSIONSDespite known limitations, fsMRI may serve as a useful diagnostic and surveillance tool for CM-I. It is more cost-effective than full conventional brain MRI and decreases the need for sedation in young children.

Cranial bone repair is one of the oldest neurosurgical practices. Reconstructing the natural contours of the skull has challenged the ingenuity of surgeons from antiquity to the present day. Given the continuous improvement of neurosurgical and emergency care over the past century, more patients survive such head injuries, thus necessitating more than ever before a simple, safe, and durable means of correcting skull defects. In response, numerous techniques and materials have been devised as the art of cranioplasty has progressed. Although the goals of cranioplasty remain the same, the evolution of techniques and diversity of materials used serves as testimony to the complexity of this task. This paper highlights the evolution of these materials and techniques, with a particular focus on the implications for managing pediatric calvarial repair and emerging trends within the field.

OBJECTIVETopical antimicrobial compounds are safe and can reduce cost and complications associated with surgical site infections (SSIs). Topical vancomycin has been an effective tool for reducing SSIs following routine neurosurgical procedures in the spine and following adult craniotomies. However, widespread adoption within the pediatric neurosurgical community has not yet occurred, and there are no studies to report on the safety and efficacy of this intervention. The authors present the first institution-wide study of topical vancomycin following open craniotomy in the pediatric population.METHODSIn this retrospective study the authors reviewed all open craniotomies performed over a period from 05/2014 to 12/2016 for topical vancomycin use, SSIs, and clinical variables associated with SSI. Topical vancomycin was utilized as an infection prophylaxis and was applied as a liquid solution following replacement of a bone flap or after dural closure when no bone flap was reapplied.RESULTSOverall, 466 consecutive open craniotomies were completed between 05/2014 and 12/2016, of which 43% utilized topical vancomycin. There was a 1.5% SSI rate in the nontopical cohort versus 0% in the topical vancomycin cohort (p = 0.045). The number needed to treat was 66. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated with topical vancomycin use.CONCLUSIONSRoutine topical vancomycin administration during closure of open craniotomies can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.

Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.

BACKGROUND AND PURPOSE: Reduced cerebral perfusion has been observed with elevated intracranial pressure. We hypothesized that arterial spin-labeled CBF can be used as a marker for symptomatic hydrocephalus. MATERIALS AND METHODS: We compared baseline arterial spin-labeled CBF in 19 children (median age, 6.5 years; range, 1–17 years) with new posterior fossa brain tumors and clinical signs of intracranial hypertension with arterial spin-labeled CBF in 16 age-matched controls and 4 patients with posterior fossa tumors without ventriculomegaly or signs of intracranial hypertension. Measurements were recorded in the cerebrum at the vertex, deep gray nuclei, and periventricular white matter and were assessed for a relationship to ventricular size. In 16 symptomatic patients, we compared cerebral perfusion before and after alleviation of hydrocephalus. RESULTS: Patients with uncompensated hydrocephalus had lower arterial spin-labeled CBF than healthy controls for all brain regions interrogated (P < .001). No perfusion difference was seen between asymptomatic patients with posterior fossa tumors and healthy controls (P = 1.000). The median arterial spin-labeled CBF increased after alleviation of obstructive hydrocephalus (P < .002). The distance between the frontal horns inversely correlated with arterial spin-labeled CBF of the cerebrum (P = .036) but not the putamen (P = .156), thalamus (P = .111), or periventricular white matter (P = .121). CONCLUSIONS: Arterial spin-labeled–CBF was reduced in children with uncompensated hydrocephalus and restored after its alleviation. Arterial spin-labeled–CBF perfusion MR imaging may serve a future role in the neurosurgical evaluation of hydrocephalus, as a potential noninvasive method to follow changes of intracranial pressure with time.

Glial cysts of the pineal gland can frequently be found in adults and children, but only rarely do they enlarge to become clinically relevant. We report a unique presentation of a pineal cyst in the midbrain tectum of a 16-month-old girl who initially presented with ptosis and strabismus. Preoperative imaging studies and intraoperative findings revealed no continuity between the tectal cyst and the pineal gland proper. We surmise that this tectal pineal cyst may have arisen from duplicated pineal gland tissue.

OBJECTIVEWhile conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus.METHODSThe authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls.RESULTSPatients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years).CONCLUSIONSDTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.

Object Focal hemosiderin deposition (FHD) is commonly observed on brain MRI scans of patients treated for childhood medulloblastoma (MB). The authors sought to determine the clinical significance of FHD and its relationship to patient age, radiation dose, and cognitive outcomes. Methods A single-institution retrospective study of 93 MB patients at Lucile Packard Children's Hospital at Stanford from 1998 to 2011 identified 41 patients with a negative baseline MRI scan and at least 2 posttreatment MRI scans obtained with T2* gradient recalled echo (GRE). The number and cumulative rate of FHDs detectable by GRE were compared between patients aged 6 years and younger (early age) and aged 7–21 years (late age) at the time of radiotherapy (RT) and between low-dose (1800–2340 cGy) and high-dose (2920–3960 cGy) RT. Results The median age at MB diagnosis was 7.3 years (range 0.9–21.0 years), the median clinical follow-up period was 5.8 years (range 0.8–13.4 years), and the median 5-year overall survival was 81% ± 7%. Of 30 school-aged children with MB, 21 (70%) required special education, and the median IQ of 10 tested patients was 100 (range 50–118). Thirty-three patients (80%) had FHD after a median latency of 1.9 years (range 0.1–5.9 years). Ninety-four percent (436 of 466) of the lesions arose in the supratentorial region of the brain, whereas 29 (6%) resided in the brainstem or the cerebellum. No spinal lesions were observed on routine spine MRI scans using T2 fast spin echo imaging. The mean cumulative lesion rate per year was 2.23 ± 3.05, and this rate was higher in older children at the time of RT compared with younger children (3.23 vs 0.67 per year, p = 0.002) but did not differ among different RT doses (p = 0.395). A child's IQ or need for special education showed no significant correlation with the rate of lesion development or number of lesions. None of the lesions resulted in symptomatic hemorrhage that required surgical intervention. Conclusions More FHD was observed in children treated for MB at the older ages than in those treated at the younger ages. There was no significant association of the incidence of FHD with radiation dose or cognitive outcomes, and none of the lesions required surgical intervention.

BACKGROUND AND PURPOSE: Injury to the dentatothalamic pathway that originates in the cerebellum has been suggested as a mechanism for neurologic complications in children treated for posterior fossa tumors. We hypothesized that time-dependent changes occur in the dentatothalamic pathway. MATERIALS AND METHODS: Diffusion tensor evaluation was performed in 14 children (median age, 4.1 years; age range, 1–20 years) who underwent serial MR imaging at 3T as part of routine follow-up after posterior fossa tumor resection with or without adjuvant therapy. Tensor metrics were obtained in the acute (≤1 week), subacute (1 to

Object Pediatric primary spinal cord tumors (PSCTs) are rare, with limited comprehensive data regarding incidence and patterns of diagnosis and treatment. The authors evaluated trends in the diagnosis and treatment of PSCTs using a nationwide database. Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for the years 1975–2007, evaluating clinical patterns in 330 patients 19 years of age or younger in whom a pediatric PSCT had been diagnosed. Histological diagnoses were grouped into pilocytic astrocytoma, other low-grade astrocytoma, ependymoma, and high-grade glioma. Patient demographics, tumor pathology, use of external beam radiation (EBR), and overall survival were analyzed. Results The incidence of pediatric PSCT was 0.09 case per 100,000 person-years and did not change over time. Males were more commonly affected than females (58% vs 42%, respectively; p < 0.006). Over the last 3 decades, the specific diagnoses of pilocytic astrocytoma and ependymoma increased, whereas the use of EBR decreased (60.6% from 1975 to 1989 vs 31.3% from 1990 to 2007; p < 0.0001). The 5- and 10-year survival rates did not differ between these time periods. Conclusions While the incidence of pediatric PSCT has not changed over time, the pattern of pathological diagnoses has shifted, and pilocytic astrocytoma and ependymoma have been increasingly diagnosed. The use of EBR over time has declined. Relative survival of patients with low-grade PSCT has remained high regardless of the pathological diagnosis.

Object Magnetic resonance imaging is commonly used in diagnosis and surveillance for optic pathway glioma (OPG). The authors investigated the role of diffusion tensor (DT) tractography in assessing the location of visual pathway fibers in the presence of tumor. Methods Data in 10 children with OPG were acquired using a 3T MRI generalized autocalibrating parallel acquisitions DT–echo planar imaging sequence (25 isotropic directions with a b value of 1000 seconds/mm2, slice thickness 3 mm). Fiber tractography was performed, with seed regions placed within the optic chiasm and bilateral nerves on the coronal plane, including the tumor and surrounding normal-appearing tissue. Tracking was performed with a curvature threshold of 30°. Results For prechiasmatic lesions, fibers either stopped abruptly at the tumor or traversed abnormally dilated nerve segments. Similar findings were seen with chiasmatic lesions, with an additional arrangement in which fibers diverged around the tumor. For each patient, DT tractography provided additional information about visual fiber arrangement in relation to the tumor that was not evident by using conventional MRI methods. Retrospective reconstruction of visual fibers in 1 patient with new postoperative hemianopia revealed an unexpected superior displacement of the optic tract that might have been helpful information had it been applied to preoperative planning or surgical navigation. Conclusions Optic pathway DT tractography is feasible in patients with OPG and provides new information about the arrangement of visual fibers in relation to tumors that could be incorporated into surgical navigation for tumor biopsy or debulking procedures.

Object Intractable epilepsy following successful brain tumor surgery in children may have several underlying causes such as residual tumor, cortical dysplasia, and gliosis. The authors reviewed the cases of children who had previously undergone resection of a brain tumor only to have medically refractory seizures postoperatively. Methods The authors performed a retrospective case review of 9 children who underwent brain tumor surgery 2–13 years before undergoing a second surgery to try and control their seizures. Results Eight of 9 children had seizures at the time of tumor presentation. Tumor types included ganglioglioma, dysembryoplastic neuroepithelial tumor, pilocytic astrocytoma, oligodendroglioma, ependymoma, and choroid plexus papilloma. All patients achieved a seizure-free interval before intractable seizures recurred. After the second operation, 3 children were seizure free, 1 only had auras, 2 had rare complex partial seizures, and 3 continued to have relatively frequent seizures, although the frequency and severity were reduced. Seven of 9 patients had pathology showing residual tumor. Conclusions Epilepsy surgery following earlier brain tumor surgery can provide substantial benefit with reduced seizure number and severity. Despite reassuring brain imaging results, residual tumor was present more often than expected in pathological specimens.

Fronto-orbital advancement is a procedure commonly performed in craniofacial centers for coronal and metopic suture synostosis. Several variations of the technique have been reported.To describe our modifications to the anterior cranioplasty procedure and the results of our surgical series.Using our craniofacial database, we retrospectively analyzed the records of all patients undergoing fronto-orbital advancement for craniosynostosis. The same team of neurosurgeons and plastic surgeons performed all procedures. Demographic data, operative time, blood loss, length of stay, and clinical outcome were analyzed.Of 248 patients treated for craniosynostosis, a total of 70 patients underwent fronto-orbital advancement. Nineteen presented with metopic, 26 with unilateral coronal, 17 with bilateral coronal, and 8 with multiple synostosis. Median age at surgery was 6.5 months. Mean operative time was 210 minutes; mean blood loss was 167 mL; and length of stay was 4.5 days. A positive correlation was found between operative time and blood loss (r = 0.1, P.01) and age at surgery and blood loss (r = 0.3, P.0001). There was a minor morbidity rate of 2.9%. A good reconstruction was obtained in all patients using our en bloc fronto-orbital advancement without any midline osteotomies at a mean follow-up of 15 months.A team approach and the application of a standardized surgical technique should make it safer to operate in young children, shorten the surgical time, and lead to a reduction in blood loss. Reconstructing the frontal bone as an entire unit yielded excellent correction for coronal and metopic synostosis.

Background/Aims: To review the pathological distribution of pediatric primary skull tumors, and to determine the diagnostic value of lesion location, patient age and lesion size. Methods: A retrospective chart review identified 51 consecutive pediatric patients with 54 primary skull tumors, treated between 2005 and 2010. Results: The most common diagnoses were dermoid cysts (n = 34) and fibrous dysplasia (n = 5). While dermoid tumors could reside anywhere (sensitivity = 0.41), a midline lesion had a specificity of 0.9 and a positive predictive value of 0.88. All of the fibrous dysplasia lesions were laterally placed, with a negative predictive value (NPV) of 1. Patient age < or >5 years had a high sensitivity and NPV for dermoid cysts and fibrous dysplasia, respectively. Size appeared to be sensitive (0.91, 0.8), but not specific (0.6, 0.78), with good NPV (0.8, 0.97) when considering dermoid cysts (≤2 cm) or fibrous dysplasia (>2 cm), respectively.Conclusion:Dermoid cysts followed by fibrous dysplasia are the most common primary skull tumors. Lesion location, patient age and lesion size give important clues as to the diagnosis. For the majority of cases, a clinical diagnosis based on CT is sufficient for presurgical evaluation.

Chordomas are malignant neoplasms that typically arise in the axial spine and primarily affect adults. When chordomas arise in pediatric patients they are more likely to display unusual histological features and aggressive behavior. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry in an index case of poorly differentiated chordoma of the sacrum, leading us to further examine SMARCB1/INI1 expression as well as that of brachyury, a highly specific marker of notochordal differentiation, in 3 additional poorly differentiated chordomas of the clivus, 10 typical chordomas, and 8 atypical teratoid/rhabdoid tumors (AT/RTs). All 4 poorly differentiated chordomas and all AT/RTs lacked nuclear expression of SMARCB1/INI1, while the 10 typical chordomas maintained strong nuclear SMARCB1/INI1 immunoreactivity. All 10 typical and 4 poorly differentiated chordomas expressed brachyury; all 8 AT/RTs were brachyury immunonegative. Cytogenetic evaluation utilizing FISH probes near the SMARCB1/INI1 locus on chromosome 22q was also performed in all of the poorly differentiated chordomas in this series. Three of the four poorly differentiated chordomas had evidence for deletion of this region by FISH. Analysis of the SMARCB1/INI1 gene sequence was performed using formalin-fixed paraffin-embedded tissue in all cases and no point mutations were observed. In summary, all poorly differentiated chordomas in this series showed the absence of SMARCB1/INI1 expression, and were reliably distinguished from AT/RTs, clinically by their characteristic primary sites of origin and pathologically by strong nuclear brachyury expression. Our findings reveal a likely role for SMARCB1/INI1 in a subset of chordomas with aggressive features.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder that occurs most commonly in the pediatric population as a result of pathological clonal proliferation of Langerhans cells with subsequent damage and destruction to surrounding tissue. Clinically, LCH presents in a variety of ways, which often results in prolonged time to diagnosis and subsequently poorer outcomes. In this case report, the authors describe an unusually early presentation of multisystem LCH in a patient at birth, which resulted in a 5-month delay to diagnosis and treatment. This patient presented both atypically young and with an uncommon initial manifestation of multisystem disease with multiple soft-tissue swellings rather than early skin involvement. Additionally, this patient had an unusual radiographic appearance with biparietal skull destruction on initial skull radiographs and biparietal soft-tissue lesions on CT resembling cephalohematoma at 3 months of age. The clinical and radiological evaluation, pathology, and treatment strategies are discussed, with particular attention paid to the importance of further workup of atypical nonresolving cephalohematomas to prevent disease progression and poorer outcomes.

To assess the tolerability and efficacy of liposomal cytarabine (LC), an encapsulated, sustained-release, intrathecal (IT) formulation of cytosine arabinoside, in de novo and relapsed central nervous system (CNS) embryonal tumors in children and young adults. We studied retrospectively all patients less than age 30 at our institution treated consecutively with LC for medulloblastoma (MB), primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Seventeen patients received LC (2 mg/kg up to 50 mg, every 2 weeks to monthly) at diagnosis of high-risk CNS embryonal tumor (2 PNET, 3 ATRT) or relapse of MB (12 MB; 9 had leptomeningeal metastases). Sixteen patients received concurrent systemic chemotherapy. A total of 108 doses were administered (IT 82, intraventricular 26) with a mean of six (range 1-16) treatments per patient. Only three administrations were associated with adverse effects of arachnoiditis or headache. None developed malignant cerebrospinal fluid (CSF) cytology while receiving LC. All the six evaluable patients with malignant CSF cytology and treated with at least two doses cleared their CSF (mean 3 doses, range 1-5). Median overall survival in relapse patients was 9.1 months. Five patients (4 de novo and 1 relapsed) remain alive in complete remission for a median 26.8 months from first LC. Liposomal cytarabine is an easily administered, well-tolerated, and active drug in patients with high-risk embryonal neoplasms. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of LC in newly diagnosed or recurrent CNS embryonal tumors.

Childhood meningiomas are rare and display important differences from adult forms. We report the first case of an intraventricular metaplastic meningioma arising in a child. A 7-year-old female underwent resection of an enhancing tumor arising within the left lateral ventricle. It was composed of monomorphic cells embedded within an abundant myxoid stroma. The cells demonstrated epithelial membrane antigen and vimentin immunoreactivity. Ultrastructural analysis demonstrated intermediate filaments, complex intercellular interdigitations and desmosomes, and a diagnosis of myxoid (metaplastic) meningioma was rendered. This case reflects the higher incidence of intraventricular meningiomas in childhood and greater incidence of intraventricular meningiomas in the left lateral ventricle. Recognition of the grade I myxoid meningioma in this case is paramount since chordoid meningiomas, which share similar histologic features, are of a higher grade and worse prognosis.

The authors describe the case of a 13-year-old boy who presented with an intraventricular hemorrhage caused by a left trigonal arteriovenous malformation. After an initial recovery, the patient experienced complete right-sided paresis on posthemorrhage Day 6. Severe cerebral vasospasm was found on MR angiography and confirmed on conventional cerebral angiography. Intraarterial nicardipine injection and balloon angioplasty were successfully performed with improved vasospasm and subsequent neurological recovery. Cerebral vasospasm should be considered in the differential diagnosis for neurological deterioration following an arteriovenous malformation hemorrhage, and aggressive treatment can be administered to prevent ischemia and further neurological deficits.

Intramedullary spinal cord tumors constitute a small fraction of central nervous system tumors in the pediatric population; of these, the majority are ependymomas or astrocytomas. We report 2 pediatric spinal cord tumor cases with unique morphologic and immunohistochemical features. The first patient presented at age 7 with an intramedullary tumor of the thoracic spine. She suffered lumbar, cerebellar, and temporal lobe recurrences despite surgical resection and radiation. The second patient presented at age 17 with an intramedullary tumor of the cervical spine. The tumor recurred locally and in the cerebellum. Magnetic resonance imaging studies demonstrated gadolinium enhancement in each case. Microscopy showed papillary and solid cytoarchitecture with monomorphous epithelioid cells arranged around vascular papillae. Immunohistochemistry in each case revealed diffuse epithelial membrane antigen, cytokeratin, and E-cadherin reactivity. Glial fibrillary acidic protein staining was focal in case 1 and completely negative in case 2. Neural cell adhesion molecule showed patchy membranous reactivity and synaptophysin was negative. Electron microscopy showed ependymal differentiation. The clinical features, including propensity for recurrence and remote subarachnoid spread, and the pathologic features of these tumors are reminiscent of papillary tumor of the pineal region, ependymoma, and choroid plexus papilloma. The cases presented may constitute a new neoplastic entity within the recently described spectrum of central nervous system tumors with ependymal features.

Object Previous investigations of health outcome after spinal surgery for tethered cord syndrome (TCS) have been single-institution studies. The aim of this study was to report inpatient complications and outcomes on a nationwide level. Methods The Nationwide Inpatient Sample (NIS) was used to identify patients who underwent spinal surgery for TCS in the US between 1993 and 2002. Patients who had a primary diagnosis of TCS (ICD-9 742.59) and also underwent spinal laminectomies were included in this study. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on variables such as mortality rate, nonfatal complications, LOS, and adverse outcomes in general (defined as death or discharge to an institution rather than home). Results The NIS sample included data on 9733 patients with TCS who underwent surgery. The means for mortality rate, complication rate, and LOS, respectively, were 0.0005%, 9.48%, and 5.6 days. Postoperative hemorrhages or hematomas (mean rate 2.3%) were the most common complications reported. Age and complications were the only significant predictors of adverse outcome on multivariate analysis. Patients older than 65 years had a threefold increase in risk of adverse outcome compared with patients 18 to 44 years of age. On average, one postoperative complication led to a 3-day increase in mean LOS and added more than $9000 to hospital charges. Conclusions This study provides a national perspective on inpatient complications and outcomes after spinal surgery for TCS in the United States. The authors have demonstrated the impact of age, complications, and medical comorbidities on the outcome of surgery for patients with this common disorder.

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, andengulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.