Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts.

Cerebral arachnoid cysts (ACs) are one of the most common and poorly understood types of developmental brain lesion. To begin to elucidate AC pathogenesis, we performed an integrated analysis of 617 patient-parent (trio) exomes, 152,898 human brain and mouse meningeal single-cell RNA sequencing transcriptomes and natural language processing data of patient medical records. We found that damaging de novo variants (DNVs) were highly enriched in patients with ACs compared with healthy individuals (P = 1.57 × 10-33). Seven genes harbored an exome-wide significant DNV burden. AC-associated genes were enriched for chromatin modifiers and converged in midgestational transcription networks essential for neural and meningeal development. Unsupervised clustering of patient phenotypes identified four AC subtypes and clinical severity correlated with the presence of a damaging DNV. These data provide insights into the coordinated regulation of brain and meningeal development and implicate epigenomic dysregulation due to DNVs in AC pathogenesis. Our results provide a preliminary indication that, in the appropriate clinical context, ACs may be considered radiographic harbingers of neurodevelopmental pathology warranting genetic testing and neurobehavioral follow-up. These data highlight the utility of a systems-level, multiomics approach to elucidate sporadic structural brain disease.

Management of dynamic cervical kyphosis with dorsal epidural lipomatosis: a Hirayama disease variant? Illustrative case.

BACKGROUND: Hirayama disease, a cervical myelopathy characterized most commonly by a self-limiting atrophic weakness of the upper extremities, is a rare entity, scarcely reported in the literature. Diagnosis is made by spinal magnetic resonance imaging (MRI), which typically shows loss of normal cervical lordosis, anterior displacement of the cord during flexion, and a large epidural cervical fat pad. Treatment options include observation or cervical immobilization by collar or surgical decompression and fusion. OBSERVATIONS: Here, the authors report an unusual case of a Hirayama-like disease in a young White male athlete who presented with rapidly progressive paresthesia in all 4 extremities and no weakness. Imaging showed characteristic findings of Hirayama disease as well as worsened cervical kyphosis and spinal cord compression in cervical neck extension, which has not previously been reported. Two-level anterior cervical discectomy and fusion and posterior spinal fusion improved both cervical kyphosis on extension and symptoms. LESSONS: Given the disease's self-limiting nature, and a lack of current reporting, there remains no consensus on how to manage these patients. Such findings presented here demonstrate the potentially heterogeneous MRI findings that can be observed in Hirayama disease and emphasize the utility of aggressive surgical management in young, active patients whereby a cervical collar may not be tolerated.

Hypermutated phenotype in gliosarcoma of the spinal cord.

Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma.

Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma.

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.

Genomic alterations underlying spinal metastases in pediatric H3K27M-mutant pineal parenchymal tumor of intermediate differentiation: case report.

Pediatric midline tumors are devastating high-grade lesions with a dismal prognosis and no curative surgical options. Here, the authors report the clinical presentation, surgical management, whole-exome sequencing (WES), and clonality analysis of a patient with a radically resected H3K27M-mutant pineal parenchymal tumor (PPT) and spine metastases consistent with PPT of intermediate differentiation (PPTID). They identified somatic mutations in H3F3A (H3K27M), FGFR1, and NF1 both in the original PPT and in the PPTID metastases. They also found 12q amplification containing CDK4/MDM2 and chromosome 17 loss of heterozygosity overlapping with NF1 that resulted in biallelic NF1 loss. They noted a hypermutated phenotype with increased C>T transitions within the PPTID metastases and 2p amplification overlapping with the MYCN locus. Clonality analysis detected three founder clones maintained during progression and metastasis. Tumor clones present within the PPTID metastases but not the pineal midline tumor harbored mutations in APC and TIMP2.While the majority of H3K27M mutations are found in pediatric midline gliomas, it is increasingly recognized that this mutation is present in a wider range of lesions with a varied morphological appearance. The present case appears to be the first description of H3K27M mutation in PPTID. Somatic mutations in H3F3A, FGFR1, and NF1 have been suggested to be driver mutations in pediatric midline gliomas. Their clonality and presence in over 80% of tumor cells in our patient's PPTID are consistent with similarly crucial roles in early tumorigenesis, with progression mediated by copy number variations and chromosomal aberrations involving known oncogenes and tumor suppressors. The roles of APC and TIMP2 mutations in progression and metastasis remain to be investigated.

Reduced influence of affective disorders on perioperative complication rates, length of hospital stay, and healthcare costs following spinal fusion for adolescent idiopathic scoliosis.

OBJECTIVE: In the past decade, a gradual transition of health policy to value-based healthcare has brought increased attention to measuring the quality of care delivered. In spine surgery, adolescents with scoliosis are a population particularly at risk for depression, anxious feelings, and impaired quality of life related to back pain and cosmetic appearance of the deformity. With the rising prevalence of mental health ailments, it is necessary to evaluate the impact of concurrent affective disorders on patient care after spinal surgery in adolescents. The aim of this study was to investigate the impact that affective disorders have on perioperative complication rates, length of stay (LOS), and total costs in adolescents undergoing elective posterior spinal fusion (PSF) (≥ 4 levels) for idiopathic scoliosis. METHODS: A retrospective study of the Kids' Inpatient Database for the year 2012 was performed. Adolescent patients (age range 10-17 years old) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were categorized into 2 groups at discharge: affective disorder or no affective disorder. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were assessed. The primary outcomes were perioperative complication rates, LOS, total cost, and discharge dispositions. RESULTS: There were 3759 adolescents included in this study, of whom 164 (4.4%) were identified with an affective disorder (no affective disorder: n = 3595). Adolescents with affective disorders were significantly older than adolescents with no affective disorders (affective disorder: 14.4 ± 1.9 years vs no affective disorder: 13.9 ± 1.8 years, p = 0.001), and had significantly different proportions of race (p = 0.005). Aside from hospital region (p = 0.016), no other patient- or hospital-level factors differed between the cohorts. Patient comorbidities did not differ significantly between cohorts. The number of vertebral levels involved was similar between the cohorts, with the majority of patients having 9 or more levels involved (affective disorder: 76.8% vs no affective disorder: 79.5%, p = 0.403). Postoperative complications were similar between the cohorts, with no significant difference in the proportion of patients experiencing a postoperative complication (p = 0.079) or number of complications (p = 0.124). The mean length of stay and mean total cost were similar between the cohorts. Moreover, the routine and nonroutine discharge dispositions were also similar between the cohorts, with the majority of patients having routine discharges (affective disorder: 93.9% vs no affective disorder: 94.9%, p = 0.591). CONCLUSIONS: This study suggests that affective disorders may not have a significant impact on surgical outcomes in adolescent patients undergoing surgery for scoliosis in comparison with adults. Further studies are necessary to elucidate how affective disorders affect adolescent patients with idiopathic scoliosis, which may improve provider approach in managing these patients perioperatively and at follow-up in hopes to better the overall patient satisfaction and quality of care delivered.

Correction of Sagittal Synostosis Using Three-Dimensional Planning and Maltese Cross Geometry.

There are several approaches to correct sagittal synostosis. Regardless of technique, the goals are to (1) release the fused suture and (2) impart a normocephalic head shape with resultant functional and aesthetic benefits. This article and video detail the authors' preferred technique for the treatment of sagittal synostosis. This novel method involves three-dimensional planning and an open approach to focus on immediate correction of the anteroposterior, mediolateral, and vertex dimensions, using vault remodeling, pedicled osseous ("Maltese") crosses, and corset pericranial flaps.

Impact of patient and hospital-level risk factors on extended length of stay following spinal fusion for adolescent idiopathic scoliosis.

OBJECTIVE: Health policy changes have led to increased emphasis on value-based care to improve resource utilization and reduce inpatient hospital length of stay (LOS). Recently, LOS has become a major determinant of quality of care and resource utilization. For adolescent idiopathic scoliosis (AIS), the determinants of extended LOS after elective posterior spinal fusion (PSF) remain relatively unknown. In the present study, the authors investigated the impact of patient and hospital-level risk factors on extended LOS following elective PSF surgery (≥ 4 levels) for AIS. METHODS: The Kids' Inpatient Database (KID) was queried for the year 2012. Adolescent patients (age range 10-17 years) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended hospital LOS was defined as greater than the 75th percentile for the entire cohort (> 6 days), and patients were dichotomized as having normal LOS or extended LOS. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were recorded. A multivariate logistic regression model was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS. RESULTS: Comorbidities were overall significantly higher in the extended-LOS cohort than the normal-LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and ≥ 9 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended-LOS cohort (20.3% [normal-LOS group] vs 43.5% [extended-LOS group]; p < 0.001). On average, the extended-LOS cohort incurred $18,916 more in total cost than the normal-LOS group ($54,697 ± $24,217 vs $73,613 ± $38,689, respectively; p < 0.001) and had more patients discharged to locations other than home (p < 0.001) than did patients in the normal-LOS cohort. On multivariate logistic regression, several risk factors were associated with extended LOS, including female sex, obesity, hypertension, fluid electrolyte disorder, paralysis, blood transfusion, ≥ 9 vertebrae fused, dural injury, and nerve cord injury. The odds ratio for extended LOS was 1.95 (95% CI 1.50-2.52) for patients with 1 complication and 5.43 (95% CI 3.35-8.71) for patients with > 1 complication. CONCLUSIONS: The authors' study using the KID demonstrates that patient comorbidities and intra- and postoperative complications all contribute to extended LOS after spinal fusion for AIS. Identifying multimodality interventions focused on reducing LOS, bettering patient outcomes, and lowering healthcare costs are necessary to improve the overall value of care for patients undergoing spinal fusion for AIS.

Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.

Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.

De novo MYH9 mutation in congenital scalp hemangioma.

Congenital hemangiomas are tumor-like vascular malformations with poorly understood pathogenesis. We report the case of a neonate with a massive congenital scalp hemangioma that required urgent neurosurgical removal on the second day of life because of concern for high-flow arteriovenous shunting. Exome sequencing identified a rare damaging de novo germline mutation in MYH9 (c.5308C>T, p.[Arg1770Cys]), encoding the MYH9 nonmuscle myosin IIA. MYH9 has a probability of loss-of-function intolerance (pLI) score of >0.99 and is highly intolerant to missense variation (z score = 5.59). The p.(Arg1770Cys) mutation substitutes an evolutionarily conserved amino acid in the protein's critical myosin tail domain and is predicted to be highly deleterious by SIFT, PolyPhen-2, MetaSVM, and CADD. MYH9 is a known regulator of cytokinesis, VEGF-regulated angiogenesis, and p53-dependent tumorigenesis. These findings reveal a novel association of germline de novo MYH9 mutation with congenital hemangioma.

Growth and alignment of the pediatric subaxial cervical spine following rigid instrumentation and fusion: a multicenter study of the Pediatric Craniocervical Society.

OBJECTIVE The long-term effects of surgical fusion on the growing subaxial cervical spine are largely unknown. Recent cross-sectional studies have demonstrated that there is continued growth of the cervical spine through the teenage years. The purpose of this multicenter study was to determine the effects of rigid instrumentation and fusion on the growing subaxial cervical spine by investigating vertical growth, cervical alignment, cervical curvature, and adjacent-segment instability over time. METHODS A total of 15 centers participated in this multi-institutional retrospective study. Cases involving children less than 16 years of age who underwent rigid instrumentation and fusion of the subaxial cervical spine (C-2 and T-1 inclusive) with at least 1 year of clinical and radiographic follow-up were investigated. Charts were reviewed for clinical data. Postoperative and most recent radiographs, CT, and MR images were used to measure vertical growth and assess alignment and stability. RESULTS Eighty-one patients were included in the study, with a mean follow-up of 33 months. Ninety-five percent of patients had complete clinical resolution or significant improvement in symptoms. Postoperative cervical kyphosis was seen in only 4 patients (5%), and none developed a swan-neck deformity, unintended adjacent-level fusion, or instability. Of patients with at least 2 years of follow-up, 62% demonstrated growth across the fusion construct. On average, vertical growth was 79% (4-level constructs), 83% (3-level constructs), or 100% (2-level constructs) of expected growth. When comparing the group with continued vertical growth to the one without growth, there were no statistically significant differences in terms of age, sex, underlying etiology, surgical approach, or number of levels fused. CONCLUSIONS Continued vertical growth of the subaxial spine occurs in nearly two-thirds of children after rigid instrumentation and fusion of the subaxial spine. Failure of continued vertical growth is not associated with the patient's age, sex, underlying etiology, number of levels fused, or surgical approach. Further studies are needed to understand this dichotomy and determine the long-term biomechanical effects of surgery on the growing pediatric cervical spine.

Tubular approach to minimally invasive microdiscectomy for pediatric lumbar disc herniation.

OBJECTIVE Lumbar disc herniation (LDH) in the pediatric population is rare and exhibits unique characteristics compared with adult LDH. There are limited data regarding the safety and efficacy of minimally invasive surgery (MIS) using tubular retractors in pediatric patients with LDH. Here, the outcomes of MIS tubular microdiscectomy for the treatment of pediatric LDH are evaluated. METHODS Twelve consecutive pediatric patients with LDH were treated with MIS tubular microdiscectomy at the authors' institution between July 2011 and October 2015. Data were gathered from retrospective chart review and from mail or electronic questionnaires. The Macnab criteria and the Oswestry Disability Index (ODI) were used for outcome measurements. RESULTS The mean age at surgery was 17 ± 1.6 years (range 13-19 years). Seven patients were female (58%). Prior to surgical intervention, 100% of patients underwent conservative treatment, and 50% had epidural steroid injections. Preoperative low-back and leg pain, positive straight leg raise, and myotomal leg weakness were noted in 100%, 83%, and 67% of patients, respectively. The median duration of symptoms prior to surgery was 9 months (range 1-36 months). The LDH level was L5-S1 in 75% of patients and L4-5 in 25%. The mean ± SD operative time was 90 ± 21 minutes, the estimated blood loss was ≤ 25 ml in 92% of patients (maximum 50 ml), and no intraoperative or postoperative complications were noted at 30 days. The median hospital length of stay was 1 day (range 0-3 days). The median follow-up duration was 2.2 years (range 0-5.8 years). One patient experienced reherniation at 18 months after the initial operation and required a second same-level MIS tubular microdiscectomy to achieve resolution of symptoms. Of the 11 patients seen for follow-up, 10 patients (91%) reported excellent or good satisfaction according to the Macnab criteria at the last follow-up. Only 1 patient reported a fair level of satisfaction by using the same criteria. Seven patients completed an ODI evaluation at the last follow-up. For these 7 patients, the mean ODI low-back pain score was 19.7% (SEM 2.8%). CONCLUSIONS To the authors' knowledge, this is the longest outcomes study and the largest series of pediatric patients with LDH who were treated with MIS microdiscectomy using tubular retractors. These data suggest that MIS tubular microdiscectomy is safe and efficacious for pediatric LDH. Larger prospective cohort studies with longer follow-up are needed to better evaluate the long-term efficacy of MIS tubular microdiscectomy versus other open and MIS techniques for the treatment of pediatric LDH.

Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib.

Efficacy of BRAF V600E targeted therapies in brain tumors harboring the mutation has been shown in several case reports and is currently being studied in larger clinical trials. Monotherapy with vemurafenib has been associated with significant side effects, including rashes, papillomas, and squamous cell carcinomas. Here we describe an adolescent female with anaplastic ganglioglioma and significant skin reaction to vemurafenib with subsequent tumor response and tolerance to the BRAF/MEK inhibitor combination of dabrafenib and trametinib without recurrence of previous reaction.

Human genetics and molecular mechanisms of vein of Galen malformation.

Vein of Galen malformations (VOGMs) are rare developmental cerebrovascular lesions characterized by fistulas between the choroidal circulation and the median prosencephalic vein. Although the treatment of VOGMs has greatly benefited from advances in endovascular therapy, including technical innovation in interventional neuroradiology, many patients are recalcitrant to procedural intervention or lack accessibility to specialized care centers, highlighting the need for improved screening, diagnostics, and therapeutics. A fundamental obstacle to identifying novel targets is the limited understanding of VOGM molecular pathophysiology, including its human genetics, and the lack of an adequate VOGM animal model. Herein, the known human mutations associated with VOGMs are reviewed to provide a framework for future gene discovery. Gene mutations have been identified in 2 Mendelian syndromes of which VOGM is an infrequent but associated phenotype: capillary malformation-arteriovenous malformation syndrome ( RASA1) and hereditary hemorrhagic telangiectasia ( ENG and ACVRL1). However, these mutations probably represent only a small fraction of all VOGM cases. Traditional genetic approaches have been limited in their ability to identify additional causative genes for VOGM because kindreds are rare, limited in patient number, and/or seem to have sporadic inheritance patterns, attributable in part to incomplete penetrance and phenotypic variability. The authors hypothesize that the apparent sporadic occurrence of VOGM may frequently be attributable to de novo mutation or incomplete penetrance of rare transmitted variants. Collaboration among treating physicians, patients' families, and investigators using next-generation sequencing could lead to the discovery of novel genes for VOGM. This could improve the understanding of normal vascular biology, elucidate the pathogenesis of VOGM and possibly other more common arteriovenous malformation subtypes, and pave the way for advances in the diagnosis and treatment of patients with VOGM.

Malignant Cerebellar Edema Subsequent to Accidental Prescription Opioid Intoxication in Children.

We present two recent cases of toddlers who developed malignant cerebellar edema subsequent to accidental ingestion of prescription opioids. Both children presented acute neurological decline, hydrocephalus, and tonsillar herniation requiring emergent ventricular drain placement, suboccipital craniectomy, and partial cerebellectomy. Together with several other reports, these cases suggest the existence of an uncommon yet severe syndrome of acute opioid-induced malignant cerebellar edema. We hypothesize that the condition results from a combination of primary opioid receptor-mediated changes in neuronal metabolism that are exacerbated by secondary hypoxic insult. If recognized promptly, this syndrome can be treated with emergent neurosurgical intervention with good clinical outcomes. These cases also illustrate the unintended consequences and innocent victims of the spiraling prescription opioid epidemic, which will likely increase in prevalence. Recognition of this syndrome by clinicians is thus critical.

Digenic mutations of human OCRL paralogs in Dent's disease type 2 associated with Chiari I malformation.

OCRL1 and its paralog INPP5B encode phosphatidylinositol 5-phosphatases that localize to the primary cilium and have roles in ciliogenesis. Mutations in OCRL1 cause the X-linked Dent disease type 2 (DD2; OMIM# 300555), characterized by low-molecular weight proteinuria, hypercalciuria, and the variable presence of cataracts, glaucoma and intellectual disability without structural brain anomalies. Disease-causing mutations in INPP5B have not been described in humans. Here, we report the case of an 11-year-old boy with short stature and an above-average IQ; severe proteinuria, hypercalciuria and osteopenia resulting in a vertebral compression fracture; and Chiari I malformation with cervico-thoracic syringohydromyelia requiring suboccipital decompression. Sequencing revealed a novel, de novo DD2-causing 462 bp deletion disrupting exon 3 of OCRL1 and a maternally inherited, extremely rare (ExAC allele frequency 8.4×10-6) damaging missense mutation in INPP5B (p.A51V). This mutation substitutes an evolutionarily conserved amino acid in the protein's critical PH domain. In silico analyses of mutation impact predicted by SIFT, PolyPhen2, MetaSVM and CADD algorithms were all highly deleterious. Together, our findings report a novel association of DD2 with Chiari I malformation and syringohydromyelia, and document the effects of digenic mutation of human OCRL paralogs. These findings lend genetic support to the hypothesis that impaired ciliogenesis may contribute to the development of Chiari I malformation, and implicates OCRL-dependent PIP3 metabolism in this mechanism.

Primary spinal myxopapillary ependymoma in the pediatric population: a study from the Surveillance, Epidemiology, and End Results (SEER) database.

Primary spinal myxopapillary ependymomas (MPE) in children are extremely rare. We examined the patient demographics, treatment modalities, and the associated outcomes of children with MPE using the Surveillance, Epidemiology, and End Results (SEER) national cancer database to gain a better understanding of these tumors. The SEER database (1973-2012) was used to analyze patients 21 years of age and younger with histologically confirmed MPE localized to the spinal cord or cauda equina. We analyzed patient demographics, extent of surgical resection, and radiation treatment. Overall survival was calculated using the Kaplan-Meier method. Statistical significance was defined as p < 0.05, with all data analyzed in IBM SPSS Statistics 21. 122 pediatric patients met inclusion criteria. The median age was 16 years (range 0-21) with 63 % male and 87 % Caucasian. The mean follow-up time was 4.5 years (95 % CI 3.93-5.07). Overall survival at 5 and 10 years was 97 and 95 %, respectively. We found 37 % underwent gross-total resection (GTR), 36 % subtotal resection (STR), and 27 % biopsy only. Patients who received GTR alone (n = 37) had a statistically significant increase in overall survival compared to those who received STR plus adjuvant radiation (n = 20) (Χ2 = 5.9, p < 0.05). To our knowledge, this is the largest survival analysis of pediatric patients with MPE. Overall survival is excellent at the 5 and 10-year time points; however, GTR should be the goal of treatment when possible. For patients with MPE, future studies should focus on longer follow-up, the role of radiation, and the therapeutic approach at tumor recurrence.

Adjuvant hypofractionated partial-brain radiation therapy for pediatric Ewing sarcoma brain metastases: case report.

This case report demonstrates that hypofractionated partial-brain radiation therapy with limited margins is a reasonable approach following gross tumor resection of Ewing sarcoma metastases to the brain. The patient presented with 2 intracranial metastases treated with gross-total resection followed by radiation therapy to 30 Gy in 5 fractions. The patient experienced symptomatic treatment-related inflammatory changes with resolution after receiving dexamethasone. He remains alive at 21 months of follow-up with no evidence of disease.

Multimodal evaluation of CSF dynamics following extradural decompression for Chiari malformation Type I.

OBJECT Extradural decompression is a minimally invasive technique for treating Chiari malformation Type I (CM-I) that avoids the complications of dural opening. While there is no agreement on which surgical method is optimal, mounting evidence demonstrates that extradural decompression effectively treats clinical symptoms, with a minimal reoperation rate. Neurological symptoms such as headache may be related to obstructed flow of CSF, and one aspect of successful extradural decompression is improved CSF dynamics. In this series, the authors report on their use of phase-contrast cine flow MRI to assess CSF flow as well as satisfactory decompression. METHODS The authors describe their first surgical series of 18 patients with CM-I undergoing extradural decompression and correlate clinical improvement with radiological changes. Patients were categorized as having complete, partial, or no resolution of their symptoms. Posterior fossa area, cisterna magna area, and tonsillar herniation were assessed on T2-weighted MRI, whereas improvement of CSF flow was evaluated with phase-contrast cine flow MRI. All patients received standard pre- and postoperative MRI studies; 8 (44.4%) patients had pre- and postoperative phase-contrast cine, while the rest underwent cine studies only postoperatively. RESULTS All 18 patients presented with symptomatic CM-I, with imaging studies demonstrating tonsillar herniation ≥ 5 mm, and 2 patients had associated syringomelia. All patients underwent suboccipital decompression and C-1 laminectomy with splitting of the dura. Patients with complete resolution of their symptoms had a greater relative increase in cisterna magna area compared with those with only partial improvement (p = 0.022). In addition, in those with complete improvement the preoperative cisterna magna area was smaller than in those who had either partial (0.020) or no (0.025) improvement. Ten (91%) of the 11 patients with improved flow also had improvement in their symptoms. There was 1 postoperative complication of dysphagia and dysphonia. None of the patients have required a second operation. CONCLUSIONS Extradural decompression has the potential to be the first-line treatment for CM-I but has been lacking an objective measure by which to assess surgical success as well as the need for reoperation. An increase in the CSF spaces and improved CSF dynamics may be associated with resolution of clinical symptoms. Including cine imaging as part of routine pre- and postoperative evaluation can help identify which patients are most likely to benefit from surgery.