Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Purpose: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.

Methods: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays.

High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702).

Background: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS).

Procedure: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors.

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients.

On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings.

Quantitative MRI criteria for optic pathway enlargement in neurofibromatosis type 1.

Objective: To determine quantitative size thresholds for enlargement of the optic nerve, chiasm, and tract in children with neurofibromatosis type 1 (NF1).

Methods: Children 0.5-18.

Clinical, Pathological, and Molecular Characterization of Infant Medulloblastomas Treated with Sequential High-Dose Chemotherapy.

Background: High-dose chemotherapy (HDC) strategies were developed to avoid unacceptable neurotoxicity associated with craniospinal irradiation in infants with embryonal brain tumors. However, the impact of molecular and pathological characterizations in such approaches and long-term outcome have not been widely described in young children.

Methods: We retrospectively collected information from seven North American institutions, on young children with medulloblastoma (MB) treated with sequential HDC, as per the CCG 99703 protocol.

Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the Children's Oncology Group.

Background: To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV).

Methods: Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only.

Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma.

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.

Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.

Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications.

CLINICAL AND MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF THORACOLUMBAR INTERVERTEBRAL DISK EXTRUSIONS AND PROTRUSIONS IN LARGE BREED DOGS.

Treatment recommendations differ for dogs with intervertebral disk extrusion vs. intervertebral disk protrusion. The aim of this retrospective, cross-sectional study was to determine whether clinical and magnetic resonance imaging (MRI) variables could be used to predict a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion in dogs.

Risk factors for cluster seizures in canine idiopathic epilepsy.

Cluster seizures (CS), two or more seizures within a 24-hour period, are reported in 38-77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated with CS include a reduced likelihood of achieving seizure freedom, decreased survival time and increased likelihood of euthanasia. Previous studies have found factors including breed, sex and neuter status are associated with CS in dogs with IE; however, only one UK study in a multi-breed study of CS in IE patients exists to the author's knowledge, and thus further data is required to confirm these results.

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.

Background: p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M.

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.

Pilocytic astrocytomas.

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor in children. PAs are a distinct histologic and biologic subset of glioma that have a slow growth rate and may even spontaneously regress. These tumors tend to arise in the cerebellum and chiasmatic/hypothalamic region, but can also occur in other regions of the central nervous system.

The Role of NG2 Proteoglycan in Glioma.

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain.

The impact of molecular analysis on the survival of children with embryonal tumors.

Embryonal tumors represent a heterogeneous group of malignancies characterized by poorly differentiated cells and generally aggressive behavior. Although advances in survival rates have been made in several of these tumor types, including Wilms' tumor, retinoblastoma, and medulloblastoma, survival of patients with central nervous system (CNS) embryonal tumors, including primitive neuro-ectodermal tumors (PNETs) and atypical teratoid rhabdoid tumors (AT/RT), are particularly poor. Advancing molecular analysis techniques and the development of gene expression profiles has led to the formulation of different subdivisions within many of the umbrella CNS tumor groups with clinical and prognostic implications.

Effects of a ketogenic diet on ADHD-like behavior in dogs with idiopathic epilepsy.

Objectives: Epilepsy in humans and rodent models of epilepsy can be associated with behavioral comorbidities including an increased prevalence of attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder symptoms and seizure frequency have been successfully reduced in humans and rodents using a ketogenic diet (KD). The aims of this study were (i) to describe the behavioral profile of dogs with idiopathic epilepsy (IE) while on a standardized nonketogenic placebo diet, to determine whether ADHD-like behaviors are present, and (ii) to examine the effect of a ketogenic medium chain triglyceride diet (MCTD) on the behavioral profile of dogs with idiopathic epilepsy (IE) compared with the standardized placebo control diet, including ADHD-like behaviors.

Divergent clonal selection dominates medulloblastoma at recurrence.

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%).

Unintentional Infusion of Phenylephrine into the Epidural Space.

We describe a patient who received an unintentionally prolonged epidural infusion of phenylephrine. The patient experienced no major morbidity. However, this case highlights the continuing problem of wrong-route drug administration and the urgent need to adopt route-specific connections.

Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome.

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly--foreshortening of the facial skeleton--is a discrete mutation that has been selected for in many popular dog breeds e.g.

Anaplastic Ependymoma in a Child With Sickle Cell Anemia: A Case Report Highlighting Treatment Challenges for Young Children With Central Nervous System Tumors and Underlying Vasculopathy.

A 3-year-old boy with sickle cell anemia (SCA) presented with progressive daily emesis and was found to have an anaplastic ependymoma. Radiation therapy and chemotherapy are usually employed after subtotal resections of anaplastic ependymomas, although the benefits from chemotherapy are unclear. To mitigate the risks of adjuvant treatment in this patient at risk for SCA-associated vasculopathy, renal impairment, and other end-organ damage, proton beam irradiation without chemotherapy was chosen.

Epilepsy beyond seizures: a review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs.

Epilepsy is one of the most common chronic neurological conditions in the dog, estimated to affect 0.6 to 0.75 per cent of dogs.

International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs.

Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates.

International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs.

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause.

A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation.

Among brain tumors, the BRAF (V600E) mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5 % of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAF (V600) mutation rate is 36 %.