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Sample records for subdural medulloblastoma model

  1. Chronic subdural hematoma associated with moyamoya phenomenon after radiotherapy for medulloblastoma; A case report

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    Fuse, Takahisa; Takagi, Takuji; Fukushima, Tsuneyuki; Mizuno, Shiroh; Hashimoto, Nobukazu; Suzuki, Osamu (Nagoya City Higashi General Hospital (Japan))

    1994-04-01

    A 9-year-old boy had been diagnosed at the age of 9 months as having a cerebellar medulloblastoma and had received 40 Gy of radiation therapy to the brain after removal of the tumor. Cerebral angiography at the time of initial diagnosis did not show any evidence of occlusive disease involving the internal carotid circulation. At the age of 6 years, the patient developed generalized seizures. On examination, he was drowsy and had right hemiparesis. CT scan demonstrated a low-density area in the left frontal lobe. Cerebral angiography showed a marked narrowing of the bilateral internal carotid arteries with moyamoya vessels. The patient was treated medically with aspirin (100 mg/day) and anticonvulsants. His neurological deficits improved gradually. At the age of 8 years, there was no recurrence of the tumor although a slight left subdural hematoma was seen on CT scan. On August 10, 1993, at the age of 9 years, he was admitted for treatment of a developing subdural hematoma. MRI showed a chronic subdural hematoma with thick outer and inner membranes. Cerebral angiography showed occlusion of the left internal carotid artery which fed the right frontal lobe through moyamoya vessels, marked narrowing of the right internal carotid artery distal to the ophthalmic artery, moyamoya vessels at the base, and cortical revascularization througth the ophthalmic, posterior cerebral and middle meningeal arteries. Trepanation and aspiration of the hematoma were performed. The outer membrane of the hematoma was about 2 mm thick and the hematoma cavity was filled with a partially organized hematoma. In this case, we speculate that development of the chronic subdural hematoma involved the following factors: (1) transdural external-internal carotid anastomosis after radiation-induced cerebrovasculopathy; (2) repeated mild head trauma due to gait disturbance after removal of the cerebellar tumor; and (3) administration of acetylsalicylic acid. (author).

  2. Medulloblastoma.

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    von Hoff, Katja; Rutkowski, Stefan

    2012-08-01

    The mainstay of medulloblastoma treatment is high-quality interdisciplinary collaboration in diagnosis, treatment, and aftercare by all involved disciplines. The first step in treatment of medulloblastoma is a maximal safe surgery, followed by thorough staging. Surgery should only be performed in experienced neurosurgical centers, with age-appropriate postoperative care. As optimal risk stratification is based on histopathological and neuroradiological assessments, these should be performed or confirmed by experienced specialists. Central review of histopathological subtype, as well as review of staging evaluations is highly desirable. For young children with desmoplastic/nodular (DMB), or extensive nodular medulloblastoma, craniospinal or any radiotherapy should be avoided. For young children with classic medulloblastoma (CMB), large cell, or anaplastic medulloblastoma (LC/A MB) optimized strategies with high-dose chemotherapy and autologous stem cell rescue with or without local radiotherapy are under investigation. For older clinical standard risk patients (without metastases, without postoperative residual tumor >1.5 cm(2)) with CMB or DMB, craniospinal radiotherapy with 23.4 Gy and boost to the posterior fossa to 54 Gy, followed by maintenance chemotherapy can be regarded as a standard therapy besides other currently applied regimen, such as the use of intensified chemotherapy after irradiation. Older children with LC/A MB, metastatic medulloblastoma, and/or large residual tumor can be regarded as high-risk patients and should receive intensified treatment: intensified chemotherapeutic regimen before or after radiotherapy with increased dose (36-Gy CSI normofractionated, or 40-Gy hyperfractionated) is used. For treatment to be effective, quality control of radiotherapy is of high relevance. Information on long-term sequelae is essential and appropriate multidisciplinary follow-up and support, including rehabilitation and help for reintegration, is necessary

  3. Matching mice to malignancy: molecular subgroups and models of medulloblastoma

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    Lau, Jasmine; Schmidt, Christin; Markant, Shirley L.; Taylor, Michael D.; Wechsler-Reya, Robert J.

    2012-01-01

    Introduction Medulloblastoma, the largest group of embryonal brain tumors, has historically been classified into five variants based on histopathology. More recently, epigenetic and transcriptional analyses of primary tumors have sub-classified medulloblastoma into four to six subgroups, most of which are incongruous with histopathological classification. Discussion Improved stratification is required for prognosis and development of targeted treatment strategies, to maximize cure and minimize adverse effects. Several mouse models of medulloblastoma have contributed both to an improved understanding of progression and to developmental therapeutics. In this review, we summarize the classification of human medulloblastoma subtypes based on histopathology and molecular features. We describe existing genetically engineered mouse models, compare these to human disease, and discuss the utility of mouse models for developmental therapeutics. Just as accurate knowledge of the correct molecular subtype of medulloblastoma is critical to the development of targeted therapy in patients, we propose that accurate modeling of each subtype of medulloblastoma in mice will be necessary for preclinical evaluation and optimization of those targeted therapies. PMID:22315164

  4. Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

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    Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

    2017-09-01

    Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis.

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    Bai, Ren-Yuan; Staedtke, Verena; Rudin, Charles M; Bunz, Fred; Riggins, Gregory J

    2015-04-01

    Medulloblastoma is the most common malignant brain tumor in children. Current standard treatments cure 40%-60% of patients, while the majority of survivors suffer long-term neurological sequelae. The identification of 4 molecular groups of medulloblastoma improved the clinical management with the development of targeted therapies; however, the tumor acquires resistance quickly. Mebendazole (MBZ) has a long safety record as antiparasitic in children and has been recently implicated in inhibition of various tyrosine kinases in vitro. Here, we investigated the efficacy of MBZ in various medulloblastoma subtypes and MBZ's impact on vascular endothelial growth factor receptor 2 (VEGFR2) and tumor angiogenesis. The inhibition of MBZ on VEGFR2 kinase was investigated in an autophosphorylation assay and a cell-free kinase assay. Mice bearing orthotopic PTCH1-mutant medulloblastoma allografts, a group 3 medulloblastoma xenograft, and a PTCH1-mutant medulloblastoma with acquired resistance to the smoothened inhibitor vismodegib were treated with MBZ. The survival benefit and the impact on tumor angiogenesis and VEGFR2 kinase function were analyzed. We determined that MBZ interferes with VEGFR2 kinase by competing with ATP. MBZ selectively inhibited tumor angiogenesis but not the normal brain vasculatures in orthotopic medulloblastoma models and suppressed VEGFR2 kinase in vivo. MBZ significantly extended the survival of medulloblastoma models derived from different molecular backgrounds. Our findings support testing of MBZ as a possible low-toxicity therapy for medulloblastomas of various molecular subtypes, including tumors with acquired vismodegib resistance. Its antitumor mechanism may be partially explained by inhibition of tumor angiogenesis. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Inhibition of CDK4/6 by Palbociclib Significantly Extends Survival in Medulloblastoma Patient-Derived Xenograft Mouse Models.

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    Cook Sangar, Michelle L; Genovesi, Laura A; Nakamoto, Madison W; Davis, Melissa J; Knobluagh, Sue E; Ji, Pengxiang; Millar, Amanda; Wainwright, Brandon J; Olson, James M

    2017-10-01

    Purpose: Bioinformatics analysis followed by in vivo studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis.Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets. The top hit from this analysis was validated in vivo using PDX models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice.Results: Informatics analysis identified the CDK4/6/CYCLIN D/RB pathway as a novel "druggable" pathway for multiple subgroups of medulloblastoma. Palbociclib, a highly specific inhibitor of CDK4/6, was found to inhibit RB phosphorylation and cause G1 arrest in PDX models of medulloblastoma. The drug caused rapid regression of Sonic hedgehog (SHH) and MYC-amplified group 3 medulloblastoma subcutaneous tumors and provided a highly significant survival advantage to mice bearing MYC-amplified intracranial tumors.Conclusions: Inhibition of CDK4/6 is potentially a highly effective strategy for the treatment of SHH and MYC-amplified group 3 medulloblastoma. Clin Cancer Res; 23(19); 5802-13. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

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    Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

    2017-03-01

    Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

  8. Modeling freedom from progression for standard-risk medulloblastoma: a mathematical tumor control model with multiple modes of failure

    DEFF Research Database (Denmark)

    Brodin, Nils Patrik; Vogelius, Ivan R.; Bjørk-Eriksson, Thomas

    2013-01-01

    As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published...

  9. Subdural hematoma

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    ... such as from falls Very young or very old age In infants and young children, a subdural hematoma ... the brain severe enough to cause coma and death) Persistent symptoms such as memory loss, dizziness , headache , anxiety , and difficulty concentrating Seizures Short-term or permanent ...

  10. BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma.

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    Gregory M Shackleford

    Full Text Available Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment. This model, termed BarTeL, utilizes a Barhl1 homeobox gene promoter to target expression of a bicistronic transgene encoding both the avian retroviral receptor TVA and an eGFP-Luciferase fusion protein to neonatal cerebellar granule neuron precursor (cGNP cells, which are cells of origin for the sonic hedgehog (SHH subgroup of human medulloblastomas. The Barhl1 promoter-driven transgene is expressed strongly in mammalian cGNPs and weakly or not at all in mature granule neurons. We efficiently induced bioluminescent medulloblastomas expressing eGFP-luciferase in BarTeL mice by infection of a limited number of somatic cGNPs with avian retroviral vectors encoding the active N-terminal fragment of SHH and a stabilized MYCN mutant. Detection and quantification of the increasing bioluminescence of growing tumors in young BarTeL mice was facilitated by the declining bioluminescence of their uninfected maturing cGNPs. Inclusion of eGFP in the transgene allowed enriched sorting of cGNPs from neonatal cerebella. Use of a single bicistronic avian vector simultaneously expressing both Shh and Mycn oncogenes increased the medulloblastoma incidence and aggressiveness compared to mixed virus infections. Bioluminescent tumors could also be produced by ex vivo transduction of neonatal BarTeL cerebellar cells by avian retroviruses and

  11. BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma.

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    Shackleford, Gregory M; Shi, Xiang-He; Swanson, Kimberly S; Mahdi, Min Y; Gonzalez-Gomez, Ignacio; Asgharzadeh, Shahab; D'Apuzzo, Massimo; Erdreich-Epstein, Anat; Moats, Rex A

    2016-01-01

    Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment. This model, termed BarTeL, utilizes a Barhl1 homeobox gene promoter to target expression of a bicistronic transgene encoding both the avian retroviral receptor TVA and an eGFP-Luciferase fusion protein to neonatal cerebellar granule neuron precursor (cGNP) cells, which are cells of origin for the sonic hedgehog (SHH) subgroup of human medulloblastomas. The Barhl1 promoter-driven transgene is expressed strongly in mammalian cGNPs and weakly or not at all in mature granule neurons. We efficiently induced bioluminescent medulloblastomas expressing eGFP-luciferase in BarTeL mice by infection of a limited number of somatic cGNPs with avian retroviral vectors encoding the active N-terminal fragment of SHH and a stabilized MYCN mutant. Detection and quantification of the increasing bioluminescence of growing tumors in young BarTeL mice was facilitated by the declining bioluminescence of their uninfected maturing cGNPs. Inclusion of eGFP in the transgene allowed enriched sorting of cGNPs from neonatal cerebella. Use of a single bicistronic avian vector simultaneously expressing both Shh and Mycn oncogenes increased the medulloblastoma incidence and aggressiveness compared to mixed virus infections. Bioluminescent tumors could also be produced by ex vivo transduction of neonatal BarTeL cerebellar cells by avian retroviruses and subsequent

  12. Use of Spongostan™ for Prevention of Cranial Subdural Adhesions Following Craniotomy in an Experimental Rabbit Model.

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    Ozdol, Cagatay; Alagoz, Fatih; Yildirim, Ali Erdem; Korkmaz, Murat; Daglioglu, Ergun; Atilla, Pergin; Muftuoglu, Sevda; Belen, Ahmet Deniz

    2015-01-01

    Spongostan™ is a sterile, water-insoluble, porcine gelatin absorbable sponge, which is widely used as a hemostatic material. The aim of this study is to test the anti-fibrotic capacity of Spongostan™, using a craniotomy model in an experimental rabbit model. Eighteen rabbits were divided into two groups: Each group consisted of 9 rabbits, duratomy plus Spongostan™ (group 1), and duratomy without Spongostan™ (group 2). Right parietal bone was removed via trephine and low speed drill and dura was opened. On the group 1 rabbits, an appropriate piece of Spongostan™ was meticulously placed under dural layer. On group 2 rabbits, same procedures were repeated without Spongostan™. Histological sections were taken from each group and evaluated for degree of fibrosis and collagen fibers. There was marked increase in number of fibroblasts and collagen fibers in group 2 rabbits, however most of the rabbits in Spongostan™ group demonstrate scarce histopathological findings for fibrosis. We conclude that an appropriately placed subdural Spongostan™ over cerebral tissue may prevent postoperative surgical adhesions after neurosurgical operations.

  13. Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

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    2017-09-01

    expansion diseases. We established the first conditional transgenic mice that express mutant human alpha-synuclein found in Parkinson’s disease...sequencing. Accomplishments: Specific Aim 1: To establish a human -iPSC-derived MYC-driven MB model and test the effects of Atoh1 expression on tumor...Atoh1+NPCs and CD133+ NSCs from human iPSCs and applied multiple markers (e.g. CD133, Atoh1, TUJ1, Sox2, Nestin) to confirm the cell identity of

  14. Cerebellum: Development and Medulloblastoma

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    Roussel, Martine F.; Hatten, Mary E.

    2011-01-01

    In the last 20 years, it has become clear that developmental genes and their regulators, noncoding RNAs including microRNAs and long-noncoding RNAs, within signaling pathways play a critical role in the pathogenesis of cancer. Many of these pathways were first identified in genetic screens in Drosophila and other lower organisms. Mammalian orthologs were subsequently identified and genes within the pathways cloned and found to regulate cell growth. The GENES and pathways expressed during embryonic development, including the Notch, Wnt/β-Catenin, TGF-β/BMP, Shh/Patched, and Hippo pathways are mutated, lost, or aberrantly regulated in a wide variety of human cancers, including skin, breast, blood, and brain cancers, including medulloblastoma. These biochemical pathways affect cell fate determination, axis formation, and patterning during development and regulate tissue homeostasis and regeneration in adults. Medulloblastoma, the most common malignant nervous system tumor in childhood, are thought to arise from disruptions in cerebellar development [reviewed by Marino, S. (2005). Medulloblastoma: Developmental mechanisms out of control. Trends Mol. Med. 11, 17–22]. Defining the extracellular cues and intracellular signaling pathways that control cerebellar neurogenesis, especially granule cell progenitor (GCP) proliferation and differentiation has been useful for developing models to unravel the mechanisms underlying medulloblastoma formation and growth. In this chapter, we will review the development of the cerebellar cortex, highlighting signaling pathways of potential relevance to tumorigenesis. PMID:21295689

  15. Evasion of cell senescence in SHH medulloblastoma.

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    Tamayo-Orrego, Lukas; Swikert, Shannon M; Charron, Frédéric

    2016-08-17

    The mechanisms leading to brain tumor formation are poorly understood. Using Ptch1+/- mice as a medulloblastoma model, sequential mutations were found to shape tumor evolution. Initially, medulloblastoma preneoplastic lesions display loss of heterozygosity of the Ptch1 wild-type allele, an event associated with cell senescence in preneoplasia. Subsequently, p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma. These findings are consistent with a model where high levels of Hedgehog signaling caused by the loss of the tumor suppressor Ptch1 lead to oncogene-induced senescence and drive p53 mutations. Thus, cell senescence is an important characteristic of a subset of SHH medulloblastoma and might explain the acquisition of somatic TP53 mutations in human medulloblastoma. This mode of medulloblastoma formation contrasts with the one characterizing Li-Fraumeni patients with medulloblastoma, where TP53 germ-line mutations cause chromothriptic genomic instability and lead to mutations in Hedgehog signaling genes, which drive medulloblastoma growth. Here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis.

  16. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

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    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  17. Cytogenetic Prognostication Within Medulloblastoma Subgroups

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    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  18. Ecto-5'-Nucleotidase Overexpression Reduces Tumor Growth in a Xenograph Medulloblastoma Model.

    Directory of Open Access Journals (Sweden)

    Angélica R Cappellari

    Full Text Available Ecto-5'-nucleotidase/CD73 (ecto-5'-NT participates in extracellular ATP catabolism by converting adenosine monophosphate (AMP into adenosine. This enzyme affects the progression and invasiveness of different tumors. Furthermore, the expression of ecto-5'-NT has also been suggested as a favorable prognostic marker, attributing to this enzyme contradictory functions in cancer. Medulloblastoma (MB is the most common brain tumor of the cerebellum and affects mainly children.The effects of ecto-5'-NT overexpression on human MB tumor growth were studied in an in vivo model. Balb/c immunodeficient (nude 6 to 14-week-old mice were used for dorsal subcutaneous xenograph tumor implant. Tumor development was evaluated by pathophysiological analysis. In addition, the expression patterns of adenosine receptors were verified.The human MB cell line D283, transfected with ecto-5'-NT (D283hCD73, revealed reduced tumor growth compared to the original cell line transfected with an empty vector. D283hCD73 generated tumors with a reduced proliferative index, lower vascularization, the presence of differentiated cells and increased active caspase-3 expression. Prominent A1 adenosine receptor expression rates were detected in MB cells overexpressing ecto-5'-NT.This work suggests that ecto-5'-NT promotes reduced tumor growth to reduce cell proliferation and vascularization, promote higher differentiation rates and initiate apoptosis, supposedly by accumulating adenosine, which then acts through A1 adenosine receptors. Therefore, ecto-5'-NT might be considered an important prognostic marker, being associated with good prognosis and used as a potential target for therapy.

  19. Giant calcified subdural empyemas.

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    Kulali, A; Erel, C; Ozyilmaz, F; Sïmsek, P

    1994-11-01

    We report two cases of chronic calcified and ossified subdural empyema diagnosed during surgery and operated on successfully using an extraordinary large osteoplastic craniotomy. After surveying the literature, we must emphasize the unusual occurrence of the chronic subdural empyemas presenting with calcification-ossification and large size as observed in both of our cases.

  20. Large calcified subdural empyema.

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    Sarkar, S; Mazumder, U; Chowdhury, D; Dey, S K; Hossain, M; Nag, U K; Riaz, B K

    2012-04-01

    Subdural empyema is a known disease entity; however, calcified subdural empyema is uncommon. The authors present a case of an 11-year-old boy in whom there was diagnosed a chronic calcified subdural empyema 10 years after an attack of meningitis. The patient had suffered from generalized tonic clonic seizures occurring 2-6 times in a month. A large fronto-temporo-parietal craniotomy was carried out and the subdural empyema filled with numerous uncharacteristic tissue fragments with thick pus together with the partially calcified and ossified capsule was removed. The empyema mass was found to be sterile for bacteria. After the operation, no epileptic seizure occurred and the boy is on sodium valporate. We must emphasize the unusual occurrence of the chronic subdural empyema presenting with calcification-ossification and large size as observed in our case.

  1. Insights into cerebellar development and medulloblastoma.

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    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  2. HDM2 promotes WIP1-mediated medulloblastoma growth

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    Buss, Meghan C.; Read, Tracy-Ann; Schniederjan, Matthew J.; Gandhi, Khanjan; Castellino, Robert C.

    2012-01-01

    Medulloblastoma is the most common malignant childhood brain tumor. The protein phosphatase and oncogene WIP1 is over-expressed or amplified in a significant number of primary human medulloblastomas and cell lines. In the present study, we examine an important mechanism by which WIP1 promotes medulloblastoma growth using in vitro and in vivo models. Human cell lines and intracerebellar xenografted animal models were used to study the role of WIP1 and the major TP53 regulator, HDM2, in medulloblastoma growth. Stable expression of WIP1 enhances growth of TP53 wild-type medulloblastoma cells, compared with cells with stable expression of an empty-vector or mutant WIP1. In an animal model, WIP1 enhances proliferation and reduces the survival of immunodeficient mice bearing intracerebellar xenografted human medulloblastoma cells. Cells with increased WIP1 expression also exhibit increased expression of HDM2. HDM2 knockdown or treatment with the HDM2 inhibitor Nutlin-3a, the active enantomer of Nutlin-3, specifically inhibits the growth of medulloblastoma cells with increased WIP1 expression. Nutlin-3a does not affect growth of medulloblastoma cells with stable expression of an empty vector or of mutant WIP1. Knockdown of WIP1 or treatment with the WIP1 inhibitor CCT007093 results in increased phosphorylation of known WIP1 targets, reduced HDM2 expression, and reduced growth specifically in WIP1 wild-type and high-expressing medulloblastoma cells. Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells. Our preclinical study supports a role for therapies that target WIP1 and HDM2 in the treatment of medulloblastoma. PMID:22379189

  3. Molecular subgroups of medulloblastoma

    Science.gov (United States)

    Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

    2014-01-01

    Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understanding of the core medulloblastoma subgroups, focusing largely on clinically relevant discoveries that have already, and will continue to, shape research. PMID:22853794

  4. Bilateral chronic subdural hematoma

    DEFF Research Database (Denmark)

    Andersen-Ranberg, Nina Christine; Rom Poulsen, Frantz; Bergholt, Bo

    2017-01-01

    OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors ar...

  5. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma.

    Science.gov (United States)

    Coni, Sonia; Mancuso, Anna Barbara; Di Magno, Laura; Sdruscia, Giulia; Manni, Simona; Serrao, Silvia Maria; Rotili, Dante; Spiombi, Eleonora; Bufalieri, Francesca; Petroni, Marialaura; Kusio-Kobialka, Monika; De Smaele, Enrico; Ferretti, Elisabetta; Capalbo, Carlo; Mai, Antonello; Niewiadomski, Pawel; Screpanti, Isabella; Di Marcotullio, Lucia; Canettieri, Gianluca

    2017-03-09

    SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB.

  6. Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Olson James M

    2011-04-01

    Full Text Available Abstract Background Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models. Methods Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo. Results Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model. Conclusions The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.

  7. Extraneural metastases in medulloblastoma

    Directory of Open Access Journals (Sweden)

    V M F Muoio

    2011-01-01

    Full Text Available Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature.

  8. BET bromodomain protein inhibition is a therapeutic option for medulloblastoma

    Science.gov (United States)

    Henssen, Anton; Thor, Theresa; Odersky, Andrea; Heukamp, Lukas; El-Hindy, Nicolai; Beckers, Anneleen; Speleman, Frank; Althoff, Kristina; Schäfers, Simon; Schramm, Alexander; Sure, Ulrich; Fleischhack, Gudrun; Eggert, Angelika; Schulte, Johannes H.

    2013-01-01

    Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications. PMID:24231268

  9. Polymicrobial subdural empyema

    DEFF Research Database (Denmark)

    Greve, Thomas; Clemmensen, Dorte; Ridderberg, Winnie

    2011-01-01

    The authors report a case of a subdural empyema (SDE) caused by a coinfection with Streptococcus intermedius and Streptococcus pneumoniae, initially considered a S. intermedius infection only. An otherwise healthy 11-year-old female was admitted to the hospital after 5 days of illness. Symptoms....... The empyema was evacuated twice, day 8 and 18, with good results. Primary samples showed growth of S. intermedius only. The severity of the clinical picture elicited supplementary samples, which were additionally positive for S. pneumoniae by an in-house specific lytA PCR and/or a commercial antigen test....

  10. Intertumoral Heterogeneity within Medulloblastoma Subgroups.

    Science.gov (United States)

    Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

    2017-06-12

    While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

    Science.gov (United States)

    Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

    2016-06-01

    Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

  12. Loss of Pin1 Suppresses Hedgehog-Driven Medulloblastoma Tumorigenesis.

    Science.gov (United States)

    Xu, Tao; Zhang, Honglai; Park, Sung-Soo; Venneti, Sriram; Kuick, Rork; Ha, Kimberly; Michael, Lowell Evan; Santi, Mariarita; Uchida, Chiyoko; Uchida, Takafumi; Srinivasan, Ashok; Olson, James M; Dlugosz, Andrzej A; Camelo-Piragua, Sandra; Rual, Jean-François

    2017-03-01

    Medulloblastoma is the most common malignant brain tumor in children. Therapeutic approaches to medulloblastoma (combination of surgery, radiotherapy, and chemotherapy) have led to significant improvements, but these are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed. Genetic mutations leading to the activation of the Hedgehog pathway drive tumorigenesis in ~30% of medulloblastoma. In a yeast two-hybrid proteomic screen, we discovered a novel interaction between GLI1, a key transcription factor for the mediation of Hedgehog signals, and PIN1, a peptidylprolyl cis/trans isomerase that regulates the postphosphorylation fate of its targets. The GLI1/PIN1 interaction was validated by reciprocal pulldowns using epitope-tagged proteins in HEK293T cells as well as by co-immunoprecipiations of the endogenous proteins in a medulloblastoma cell line. Our results support a molecular model in which PIN1 promotes GLI1 protein abundance, thus contributing to the positive regulation of Hedgehog signals. Most importantly, in vivo functional analyses of Pin1 in the GFAP-tTA;TRE-SmoA1 mouse model of Hedgehog-driven medulloblastoma demonstrate that the loss of Pin1 impairs tumor development and dramatically increases survival. In summary, the discovery of the GLI1/PIN1 interaction uncovers PIN1 as a novel therapeutic target in Hedgehog-driven medulloblastoma tumorigenesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Imaging Biomarkers for Adult Medulloblastomas

    DEFF Research Database (Denmark)

    Keil, V C; Warmuth-Metz, M; Reh, C

    2017-01-01

    BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences...... in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists......-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study. RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six...

  14. Medulloblastoma: From Myth to Molecular.

    Science.gov (United States)

    Ramaswamy, Vijay; Taylor, Michael D

    2017-07-20

    Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric. Distinguishing the four molecular subgroups of medulloblastoma-wingless (WNT), sonic hedgehog (SHH), group 3, and group 4-in the daily treatment of patients, as well in the setting of clinical trials, is an important challenge in the near term for the pediatric neuro-oncology community. The preponderance of morbidity in treating patients with medulloblastoma is secondary to the treatment or prophylaxis of leptomeningeal metastases, and the cause of most deaths is leptomeningeal metastases. Recurrence of medulloblastoma is a nearly universally fatal event, with no significant salvage rate. The extent of spatial and temporal intratumoral heterogeneity as medulloblastoma metastasizes to leptomeninges and as it evolves in the face of radiation and cytotoxic chemotherapy is just beginning to be understood as a major barrier to therapeutic success. Pediatric neuro-oncology clinicians and scientists must now determine how best to incorporate rapid changes in our biologic understanding of medulloblastoma into the next generation of upfront clinical trials, with the goal of both improving survival for the highest-risk patients and improving quality of life for survivors.

  15. Mozart's chronic subdural hematoma.

    Science.gov (United States)

    Drake, M E

    1993-11-01

    No commemoration of the bicentennial of Mozart's death would be complete without some consideration of that premature yet predictable demise. Mozart's premonitions of death are well known and apparently played a role in the composition of the K.626 Requiem and perhaps other works. His death has traditionally been ascribed to infectious causes, chiefly rheumatic fever or post-streptococcal glomerulonephritis, exacerbated by intemperance and chronic penury. Pathology has been difficult because of his supposed burial in a pauper's grave, the location and contents of which were later supposedly lost. Mozart's burial place in St. Mark's Cemetery in Vienna was known and, in the parlance of the day, "reorganized" a decade later, as the occupants of plots were disinterred to make room for the more recently decreased. A skull believed to the Mozart's was saved by the successor of the gravedigger who had supervised Mozart's burial, and then passed into the collections of the anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg). Forensic reconstruction of soft tissues related to this skull reveals substantial concordance with Mozart's portraits. The skull suggests premature closure of the metopic suture, which has been suggested on the basis of his physiognomy. A left temporal fracture and concomitant erosions raise the question of chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting he experienced in 1790 and 1791. Aggressive bloodletting to treat suspected rheumatic fever could have decompensated such a lesion to produce his death on December 5, 1791.

  16. Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma

    Science.gov (United States)

    Balakrishnan, Ilango; Harris, Peter; Birks, Diane K; Griesinger, Andrea; Amani, Vladimir; Cristiano, Brian; Remke, Marc; Taylor, Michael D; Handler, Michael; Foreman, Nicholas K; Vibhakar, Rajeev

    2014-01-01

    Medulloblastoma is a pediatric brain tumor with a variable prognosis due to clinical and genomic heterogeneity. Among the 4 major genomic sub-groups, patients with MYC amplified tumors have a particularly poor prognosis despite therapy with surgery, radiation and chemotherapy. Targeting the MYC oncogene has traditionally been problematic. Here we report that MYC driven medulloblastoma can be targeted by inhibition of the bromodomain protein BRD4. We show that bromodomain inhibition with JQ1 restricts c-MYC driven transcriptional programs in medulloblastoma, suppresses medulloblastoma cell growth and induces a cell cycle arrest. Importantly JQ1 suppresses stem cell associated signaling in medulloblastoma cells and inhibits medulloblastoma tumor cell self-renewal. Additionally JQ1 also promotes senescence in medulloblastoma cells by activating cell cycle kinase inhibitors and inhibiting activity of E2F1. Furthermore BRD4 inhibition displayed an anti-proliferative, pro-senescence effect in a medulloblastoma model in vivo. In clinical samples we found that transcriptional programs suppressed by JQ1 are associated with adverse risk in medulloblastoma patients. Our work indicates that BRD4 inhibition attenuates stem cell signaling in MYC driven medulloblastoma and demonstrates the feasibility BET domain inhibition as a therapeutic approach in vivo. PMID:24796395

  17. Hidroma subdural na fossa posterior

    Directory of Open Access Journals (Sweden)

    José Carlos Vasques

    1970-03-01

    Full Text Available Os autores relatam um caso de hidroma subdural na fossa craniana posterior conseqüente a traumatismo na região occipital. O paciente foi operado com pleno sucesso. A raridade da localização de hidroma na fossa posterior é salientada, sendo discutidos os possíveis mecanismos etio-patogênicos.

  18. Acute Subdural Hematoma

    Directory of Open Access Journals (Sweden)

    Ellen Lester

    2017-04-01

    Full Text Available History of present illness: A 21-year-old female with no past medical history presented to the ED after multiple tonic-clonic seizures over the previous 12 hours, the longest lasting 20 seconds. She returned to baseline after each seizure, had no obvious signs of trauma, and did not exhibit any focal neurologic deficits. She denied illicit drugs or new medications. A family member noted that she had fallen from her bed (approximately 3 feet high 2 days ago. Significant findings: Non-contrast Computed Tomography (CT of the Head showed a dense extra-axial collection along the left frontal and parietal regions, extending superior to the vertex with mild mass effect, but no midline shift. Discussion: Intracranial hemorrhage (ICH is a term to describe any abnormal bleeding within the bony confines of the skull. Most commonly, subdural hemorrhages (SDH result from injury to the bridging veins that lead to bleeding between the dura and arachnoid maters. However, in 20%-30% of cases an arterial source of bleeding can be found.1 For adults, motor vehicle collisions and other unintentional head trauma are typically the provoking factors in developing SDH. Falls in the elderly are a common cause of SDH since diffuse cerebral atrophy leads to increased shear forces upon vasculature structures during the fall. The risk of SDH increases with the use of anti-thrombotic agents.2 Clinical presentation varies from asymptomatic to coma (in 50 percent of acute SDH. Chronic SDH may present with headaches, light-headedness, cognitive impairment, and seizures.1 The risk of posttraumatic epileptic seizures (PTS is higher in acute SDH. Risk factors for acute SDH PTS include low Glasgow Coma Score and craniotomy, whereas risk factors for PTS in chronic SDH include alcohol abuse, change in mental status, previous stroke, and hematoma density on CT.3 CT is the most widely used imaging modality for identifying ICH. Acute SDH (within 1-2 days are visualized as hyperdense

  19. Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans.

    Science.gov (United States)

    Pöschl, J; Lorenz, A; Hartmann, W; von Bueren, A O; Kool, M; Li, S; Peraud, A; Tonn, J-C; Herms, J; Xiang, M; Rutkowski, S; Kretzschmar, H A; Schüller, U

    2011-11-24

    Medulloblastoma is the most common malignant brain tumor in childhood, and development of targeted therapies is highly desired. Although the molecular mechanisms of malignant transformation are not fully understood, it is known that medulloblastomas may arise from cerebellar granule neuron precursors. The homeodomain transcription factor Barhl1 is known to regulate migration and survival of granule cell precursors, but its functional role in medulloblastoma is unknown. We show here that the expression of BARHL1 is significantly upregulated during human cerebellar development and in human medulloblastoma samples as compared with the normal adult cerebellum. We also detected high levels of Barhl1 expression in medulloblastomas of Math1-cre:SmoM2 mice, a mouse model for Sonic hedgehog-associated medulloblastomas that we developed previously. To investigate Barhl1 function in vivo during tumor development, we generated Barhl1(-/-)Math1-cre:SmoM2 mice. Interestingly, tumors that developed in these mice displayed increased mitotic activity and decreased neuronal differentiation. Moreover, survival of these mice was significantly decreased. Similarly, low expression of BARHL1 in human medulloblastoma cases was associated with a less favorable prognosis for patients. These results suggest that the expression of Barhl1 decelerates tumor growth both in human and in murine medulloblastomas and should be further investigated with respect to potential implications for individualized therapeutic strategies.

  20. TAp73 is a marker of glutamine addiction in medulloblastoma.

    Science.gov (United States)

    Niklison-Chirou, Maria Victoria; Erngren, Ida; Engskog, Mikael; Haglöf, Jakob; Picard, Daniel; Remke, Marc; McPolin, Phelim Hugh Redmond; Selby, Matthew; Williamson, Daniel; Clifford, Steven C; Michod, David; Hadjiandreou, Michalis; Arvidsson, Torbjörn; Pettersson, Curt; Melino, Gerry; Marino, Silvia

    2017-09-01

    Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma. © 2017 Niklison-Chirou et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

    Science.gov (United States)

    Hooper, Cornelia M.; Hawes, Susan M.; Kees, Ursula R.; Gottardo, Nicholas G.; Dallas, Peter B.

    2014-01-01

    Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10–15 and 20–30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies. PMID:25412507

  2. Receiver operating characteristic curve analysis of SEER medulloblastoma and primitive neuroectodermal tumor (PNET) outcome data: identification and optimization of predictive models.

    Science.gov (United States)

    Cheung, Min Rex

    2014-01-01

    This study used receiver operating characteristic curves to analyze Surveillance, Epidemiology and End RESULTS (SEER) medulloblastoma (MB) and primitive neuroectodermal tumor (PNET) outcome data. The aim of this study was to identify and optimize predictive outcome models. Patients diagnosed from 1973 to 2009 were selected for analysis of socio-economic, staging and treatment factors available in the SEER database for MB and PNET. For the risk modeling, each factor was fitted by a generalized linear model to predict the outcome (brain cancer specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A Monte Carlo algorithm was used to estimate the modeling errors. There were 3,702 patients included in this study. The mean follow up time (S.D.) was 73.7 (86.2) months. Some 40% of the patients were female and the mean (S.D.) age was 16.5 (16.6) years. There were more adult MB/PNET patients listed from SEER data than pediatric and young adult patients. Only 12% of patients were staged. The SEER staging has the highest ROC (S.D.) area of 0.55 (0.05) among the factors tested. We simplified the 3-layered risk levels (local, regional, distant) to a simpler non-metastatic (I and II) versus metastatic (III) model. The ROC area (S.D.) of the 2-tiered model was 0.57 (0.04). ROC analysis optimized the most predictive SEER staging model. The high under staging rate may have prevented patients from selecting definitive radiotherapy after surgery.

  3. Functional validation of the oncogenic cooperativity and targeting potential of tuberous sclerosis mutation in medulloblastoma using a MYC-amplified model cell line.

    Science.gov (United States)

    Henderson, Jacob J; Wagner, Jacob P; Hofmann, Nicolle E; Eide, Christopher A; Cho, Yoon-Jae; Druker, Brian J; Davare, Monika A

    2017-10-01

    Medulloblastoma is the most common malignant brain tumor of childhood. To identify targetable vulnerabilities, we employed inhibitor screening that revealed mTOR inhibitor hypersensitivity in the MYC-overexpressing medulloblastoma cell line, D341. Concomitant exome sequencing unveiled an uncharacterized missense mutation, TSC2A415V , in these cells. We biochemically demonstrate that the TSC2A415V mutation is functionally deleterious, leading to shortened half-life and proteasome-mediated protein degradation. These data suggest that MYC cooperates with activated kinase pathways, enabling pharmacologic intervention in these treatment refractory tumors. We propose that identification of activated kinase pathways may allow for tailoring targeted therapy to improve survival and treatment-related morbidity in medulloblastoma. © 2017 Wiley Periodicals, Inc.

  4. Chronic subdural haematoma complicating spinal anaesthesia: A ...

    African Journals Online (AJOL)

    Subdural haematoma is a rare but serious complication of dural puncture. We report a case of chronic subdural haematoma, which occurred following spinal anaesthesia for elective caesarean section. A 34-year-old multiparous woman presented with a post-dural puncture headache (PDPH) following spinal anaesthesia.

  5. Calcified chronic subdural hematoma: case report.

    Science.gov (United States)

    Yan, H J; Lin, K E; Lee, S T; Tzaan, W C

    1998-12-01

    Calcified or ossified chronic subdural hematoma is a rare entity that usually presents as a space-occupying lesion over the cerebral convexity. We report a case of calcified and ossified chronic subdural hematoma in an unusual location that has not been previously reported. A 24-year-old man with a history of tonic-clonic convulsions since 7 months of age was admitted because of increasing frequency and duration of seizures. Computed tomography and magnetic resonance imaging demonstrated a fusiform extra-axial lesion just above the tentorium and adjacent to the cerebral falx. A calcified and ossified chronic subdural hematoma was noted and was almost completely removed by craniotomy. Better seizure control was achieved by removal of the calcified chronic subdural hematoma. Calcified subdural hematoma, calcified epidural hematoma, calcified empyema, meningioma, calcified arachnoid cyst, and calcified convexity of the dura mater with acute epidural hematoma should be considered for the differential diagnosis of an extra-axial calcified lesion.

  6. Survival After Relapse of Medulloblastoma.

    Science.gov (United States)

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

  7. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, Erna M. C.; Schouten-van Meeteren, Antoinette Y. N.; Doz, François; Janssens, Geert O.; van Dalen, Elvira C.

    2015-01-01

    Background Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by

  8. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, E.M.; Schouten-van Meeteren, A.Y.; Doz, F.; Janssens, G.O.R.J.; Dalen, E.C. van

    2015-01-01

    BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by

  9. YB-1 is elevated in medulloblastoma and drives proliferation in Sonic hedgehog-dependent cerebellar granule neuron progenitor cells and medulloblastoma cells.

    Science.gov (United States)

    Dey, A; Robitaille, M; Remke, M; Maier, C; Malhotra, A; Gregorieff, A; Wrana, J L; Taylor, M D; Angers, S; Kenney, A M

    2016-08-11

    Postnatal proliferation of cerebellar granule neuron precursors (CGNPs), proposed cells of origin for the SHH-associated subgroup of medulloblastoma, is driven by Sonic hedgehog (Shh) and insulin-like growth factor (IGF) in the developing cerebellum. Shh induces the oncogene Yes-associated protein (YAP), which drives IGF2 expression in CGNPs and mouse Shh-associated medulloblastomas. To determine how IGF2 expression is regulated downstream of YAP, we carried out an unbiased screen for transcriptional regulators bound to IGF2 promoters. We report that Y-box binding protein-1 (YB-1), an onco-protein regulating transcription and translation, binds to IGF2 promoter P3. We observed that YB-1 is upregulated across human medulloblastoma subclasses as well as in other varieties of pediatric brain tumors. Utilizing the cerebellar progenitor model for the Shh subgroup of medulloblastoma in mice, we show for the first time that YB-1 is induced by Shh in CGNPs. Its expression is YAP-dependent and it is required for IGF2 expression in CGNPs. Finally, both gain-of function and loss-of-function experiments reveal that YB-1 activity is required for sustaining CGNP and medulloblastoma cell (MBC) proliferation. Collectively, our findings describe a novel role for YB-1 in driving proliferation in the developing cerebellum and MBCs and they identify the SHH:YAP:YB1:IGF2 axis as a powerful target for therapeutic intervention in medulloblastomas.

  10. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.

    Science.gov (United States)

    Phoenix, Timothy N; Patmore, Deanna M; Boop, Scott; Boulos, Nidal; Jacus, Megan O; Patel, Yogesh T; Roussel, Martine F; Finkelstein, David; Goumnerova, Liliana; Perreault, Sebastien; Wadhwa, Elizabeth; Cho, Yoon-Jae; Stewart, Clinton F; Gilbertson, Richard J

    2016-04-11

    The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Subdural injection: report of two cases

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    Cadavid-Puentes, Adriana

    2016-10-01

    Full Text Available Two cases are reported of accidental subdural injection during epidural procedures for pain control. The first one was a man with chronic lumbar pain who suffered such complication during an epidural injection of steroids using the interlaminar approach. The second one was a woman with intracranial hypotension syndrome who required the application of an epidural blood patch in order to control multiple CSF fistulae. The procedure had to be aborted twice due to the subdural pattern observed after injection of the contrast medium. Accidental subdural block is a rare complication of epidural injection for analgesic or anesthetic procedures.

  12. Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin.

    Science.gov (United States)

    Hutzen, Brian; Bid, Hemant Kumar; Houghton, Peter J; Pierson, Christopher R; Powell, Kimerly; Bratasz, Anna; Raffel, Corey; Studebaker, Adam W

    2014-03-19

    Medulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis. Oncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease. Medulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus' cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood

  13. Chronic subdural hematomas caused by vibrating Chinese ...

    African Journals Online (AJOL)

    Abstract. We present two middle aged Nigerian patients who developed significant chronic subdural hematomas weeks after going on vibrating Chinese massage chairs. This complication of using the chairs has not been previously reported.

  14. Outcome following subdural haemorrhages in infancy

    OpenAIRE

    Jayawant, Sandeep; Parr, Jeremy,

    2007-01-01

    Subdural haemorrhages (SDH) are associated with significant neurodisability in affected individuals. The incidence of SDH in infants is between 12 and 25 cases per 100 000 children and most detected SDH are due to physical abuse. In the infant brain, SDH are caused by tearing of the bridging veins in the subdural space and may result in significant brain injury. The challenge of assessing outcome in infants with SDH is evaluating whether SDH or other accompanying brain insults are instrumenta...

  15. ASPM gene expression in medulloblastoma.

    Science.gov (United States)

    Vulcani-Freitas, Tânia M; Saba-Silva, Najsla; Cappellano, Andréa; Cavalheiro, Sérgio; Marie, Sueli K N; Oba-Shinjo, Sueli M; Malheiros, Suzana M F; de Toledo, Sílvia Regina Caminada

    2011-01-01

    Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

  16. Sonic Hedgehog-Induced Histone Deacetylase Activation Is Required for Cerebellar Granule Precursor Hyperplasia in Medulloblastoma

    Science.gov (United States)

    Lee, Seung Joon; Lindsey, Stephan; Graves, Bruce; Yoo, Soonmoon; Olson, James M.; Langhans, Sigrid A.

    2013-01-01

    Medulloblastoma, the most common pediatric brain tumor, is thought to arise from deregulated proliferation of cerebellar granule precursor (CGP) cells. Sonic hedgehog (Shh) is the primary mitogen that regulates proliferation of CGP cells during the early stages of postnatal cerebellum development. Aberrant activation of Shh signaling during this time has been associated with hyperplasia of CGP cells and eventually may lead to the development of medulloblastoma. The molecular targets of Shh signaling involved in medulloblastoma formation are still not well-understood. Here, we show that Shh regulates sustained activation of histone deacetylases (HDACs) and that this activity is required for continued proliferation of CGP cells. Suppression of HDAC activity not only blocked the Shh-induced CGP proliferation in primary cell cultures, but also ameliorated aberrant CGP proliferation at the external germinal layer (EGL) in a medulloblastoma mouse model. Increased levels of mRNA and protein of several HDAC family members were found in medulloblastoma compared to wild type cerebellum suggesting that HDAC activity is required for the survival/progression of tumor cells. The identification of a role of HDACs in the early steps of medulloblastoma formation suggests there may be a therapeutic potential for HDAC inhibitors in this disease. PMID:23951168

  17. Sonic hedgehog-induced histone deacetylase activation is required for cerebellar granule precursor hyperplasia in medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Seung Joon Lee

    Full Text Available Medulloblastoma, the most common pediatric brain tumor, is thought to arise from deregulated proliferation of cerebellar granule precursor (CGP cells. Sonic hedgehog (Shh is the primary mitogen that regulates proliferation of CGP cells during the early stages of postnatal cerebellum development. Aberrant activation of Shh signaling during this time has been associated with hyperplasia of CGP cells and eventually may lead to the development of medulloblastoma. The molecular targets of Shh signaling involved in medulloblastoma formation are still not well-understood. Here, we show that Shh regulates sustained activation of histone deacetylases (HDACs and that this activity is required for continued proliferation of CGP cells. Suppression of HDAC activity not only blocked the Shh-induced CGP proliferation in primary cell cultures, but also ameliorated aberrant CGP proliferation at the external germinal layer (EGL in a medulloblastoma mouse model. Increased levels of mRNA and protein of several HDAC family members were found in medulloblastoma compared to wild type cerebellum suggesting that HDAC activity is required for the survival/progression of tumor cells. The identification of a role of HDACs in the early steps of medulloblastoma formation suggests there may be a therapeutic potential for HDAC inhibitors in this disease.

  18. The cellular and molecular biology of medulloblastoma

    NARCIS (Netherlands)

    Peringa, A; Fung, KM; Muragaki, Y; Trojanowski, JQ

    1995-01-01

    Medulloblastomas are prototypical of primitive neuroectodermal tumors which are some of the most frequent malignant brain tumors of childhood. The cell biology of medulloblastomas is still poorly understood, but recent studies of the expression of trophic factors and their receptors in

  19. Adult medulloblastoma with myogenic differentiation

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    Xia-ling ZHANG

    2015-09-01

    Full Text Available Objective To explore the clinicopathological features of adult medulloblastoma with myogenic differentiation and to discuss clinicopathological differentiations from relevant tumors, so as to improve the ability of diagnosing and differentiating this kind of tumor. Methods The clinical manifestations, imaging, pathological features and immunohistochemical features of one case of adult medulloblastoma with myogenic differentiation were analyzed, and related literatures were reviewed. Results A 32-year-old female patient presented with repeated distortion of mouth and facial numbness for over 6 years. T1WI showed a mixed-signal lesion in the cerebellar vermis and dorsal part of brainstem, and protruded toward the fourth ventricle. Enhanced T1WI showed a round strengthened nodule in the lesion. During operation, it was seen that the tumor arised in cerebellar vermis, projected into the fourth ventricle and invaded brainstem. On microscopy examination, it was found that oval nuclei tumor cells were distributed in sheet or scattered patterns, and neuroblastic rosettes were observed. Abundant and eosinophilic cytoplasm, eccentrically placed and atypical nuclei containing hyperchromatic chromatin or prominent nucleoli in the tumor could be displayed. Mitoses were frequently seen. The tumor also presented with fresh and old hemorrhage in some place. Immunohistochemical staining showed that tumor cells were diffusely positive for integrase interactor 1 (INI1, synaptophysin (Syn, chromogranin A (CgA, human internexin neuronal intermediate filament protein α (INα, neurofilament protein (NF, Nestin (Nes, β-catenin and P53, and partly positive for desmin (Des, neuronal nuclei (NeuN and S-100 protein (S-100, but negative for glial fibrillary acidic protein (GFAP, oligodendrocyte transcription factor-2 (Olig-2, CD99, pan cytokeratin (PCK, epithelial membrane antigen (EMA, MyoD1, myogenin, muscle-specific actin (MSA and smooth muscle actin (SMA. Ki-67

  20. Serpine2/PN-1 Is Required for Proliferative Expansion of Pre-Neoplastic Lesions and Malignant Progression to Medulloblastoma

    Science.gov (United States)

    Vaillant, Catherine; Kool, Marcel; Schwarzentruber-Schauerte, Alexandra; Méreau, Hélène; Cabuy, Erik; Lobrinus, Johannes A.; Pfister, Stefan; Zuniga, Aimée; Frank, Stephan; Zeller, Rolf

    2015-01-01

    Background Medulloblastomas are malignant childhood brain tumors that arise due to the aberrant activity of developmental pathways during postnatal cerebellar development and in adult humans. Transcriptome analysis has identified four major medulloblastoma subgroups. One of them, the Sonic hedgehog (SHH) subgroup, is caused by aberrant Hedgehog signal transduction due to mutations in the Patched1 (PTCH1) receptor or downstream effectors. Mice carrying a Patched-1 null allele (Ptch1∆/+) are a good model to study the alterations underlying medulloblastoma development as a consequence of aberrant Hedgehog pathway activity. Results Transcriptome analysis of human medulloblastomas shows that SERPINE2, also called Protease Nexin-1 (PN-1) is overexpressed in most medulloblastomas, in particular in the SHH and WNT subgroups. As siRNA-mediated lowering of SERPINE2/PN-1 in human medulloblastoma DAOY cells reduces cell proliferation, we analyzed its potential involvement in medulloblastoma development using the Ptch1∆/+ mouse model. In Ptch1∆/+ mice, medulloblastomas arise as a consequence of aberrant Hedgehog pathway activity. Genetic reduction of Serpine2/Pn-1 interferes with medulloblastoma development in Ptch1∆/+ mice, as ~60% of the pre-neoplastic lesions (PNLs) fail to develop into medulloblastomas and remain as small cerebellar nodules. In particular the transcription factor Atoh1, whose expression is essential for development of SHH subgroup medulloblastomas is lost. Comparative molecular analysis reveals the distinct nature of the PNLs in young Ptch1∆/+Pn-1Δ/+ mice. The remaining wild-type Ptch1 allele escapes transcriptional silencing in most cases and the aberrant Hedgehog pathway activity is normalized. Furthermore, cell proliferation and the expression of the cell-cycle regulators Mycn and Cdk6 are significantly reduced in PNLs of Ptch1∆/+Pn-1Δ/+ mice. Conclusions Our analysis provides genetic evidence that aberrant Serpine2/Pn-1 is required for

  1. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

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    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  2. The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for targeted medulloblastoma therapy

    Science.gov (United States)

    Holst, Martin I.; Pietsch, Torsten; Dilloo, Dagmar

    2015-01-01

    Deregulation of the Phosphoinositide 3-kinase (PI3K)/AKT signalling network is a hallmark of oncogenesis. Also medulloblastoma, the most common malignant brain tumor in children, is characterized by high levels of AKT phosphorylation and activated PI3K signalling in medulloblastoma is associated with enhanced cellular motility, survival and chemoresistency underscoring its role of as a potential therapeutic target. Here we demonstrate that GDC-0941, a highly specific PI3K inhibitor with good clinical tolerability and promising anti-neoplastic activity in adult cancer, also displays anti-proliferative and pro-apoptotic effects in pediatric human medulloblastoma cell lines. Loss in cell viability is accompanied by reduced phosphorylation of AKT, a downstream target of PI3K. Furthermore, we show that GDC-0941 attenuates the migratory capacity of medulloblastoma cells and targets subpopulations expressing the stem cell marker CD133. GDC-0941 also synergizes with the standard medulloblastoma chemotherapeutic etoposide. In an orthotopic xenograft model of the most aggressive human medulloblastoma variant we document that oral adminstration of GDC-0941 impairs tumor growth and significantly prolongs survival. These findings provide a rational to further investigate GDC-0941 alone and in combination with standard chemotherapeutics for medulloblastoma treatment. PMID:25596739

  3. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    chose to make new medulloblastoma models with oncogenic PIK3CA (PIK3CAH1047R). However, this change caused major delay in our progress since we have not...these tumors. 15. SUBJECT TERMS cancer stem cells, medulloblastoma, targeted therapy, therapy resistance , pediatric cancer, brain tumor, Notch1...Keywords……………………………………………………………. 4 3. Accomplishments………..………………………………………….. 4 4. Impact…………………………...…………………………………… 8 5. Changes /Problems

  4. Medulloblastoma stem cells: Promising targets in medulloblastoma therapy.

    Science.gov (United States)

    Huang, Guo-Hao; Xu, Qing-Fu; Cui, You-Hong; Li, Ningning; Bian, Xiu-Wu; Lv, Sheng-Qing

    2016-05-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long-term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. The CSCs are thought to be largely responsible for tumor initiation, maintenance, dissemination, and relapse; therefore, their pivotal roles have revealed them to be promising targets in MB therapy. Our growing understanding of the major medulloblastoma molecular subgroups and the derivation of some of these groups from specific stem or progenitor cells adds additional layers to the CSC knowledge base. Herein we review the current knowledge of MB stem cells, highlight the molecular mechanisms relating to MB relapse and leptomeningeal dissemination, and incorporate these with the need to develop more effective and accurate therapies for MB patients. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Uniformity under in vitro conditions: Changes in the phenotype of cancer cell lines derived from different medulloblastoma subgroups.

    Science.gov (United States)

    Chlapek, Petr; Zitterbart, Karel; Kren, Leos; Filipova, Lenka; Sterba, Jaroslav; Veselska, Renata

    2017-01-01

    Medulloblastoma comprises four main subgroups (WNT, SHH, Group 3 and Group 4) originally defined by transcriptional profiling. In primary medulloblastoma tissues, these groups are thought to be distinguishable using the immunohistochemical detection of β-catenin, filamin A, GAB1 and YAP1 protein markers. To investigate the utility of these markers for in vitro studies using medulloblastoma cell lines, immunoblotting and indirect immunofluorescence were employed for the detection of β-catenin, filamin A, GAB1 and YAP1 in both DAOY and D283 Med reference cell lines and the panel of six medulloblastoma cell lines derived in our laboratory from the primary tumor tissues of known molecular subgroups. Immunohistochemical detection of these markers was performed on formalin-fixed paraffin-embedded tissue of the matching primary tumors. The results revealed substantial divergences between the primary tumor tissues and matching cell lines in the immunoreactivity pattern of medulloblastoma-subgroup-specific protein markers. Regardless of the molecular subgroup of the primary tumor, all six patient-derived medulloblastoma cell lines exhibited a uniform phenotype: immunofluorescence showed the nuclear localization of YAP1, accompanied by strong cytoplasmic positivity for β-catenin and filamin A, as well as weak positivity for GAB1. The same immunoreactivity pattern was also found in both DAOY and D283 Med reference medulloblastoma cell lines. Therefore, we can conclude that various medulloblastoma cell lines tend to exhibit the same characteristics of protein marker expression under standard in vitro conditions. Such a finding emphasizes the importance of the analyses of primary tumors in clinically oriented medulloblastoma research and the urgent need to develop in vitro models of improved clinical relevance, such as 3D cultures and organotypic slice cultures.

  6. Reversible Parkinsonism secondary to chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Wajid Nazir Wani

    2013-01-01

    Full Text Available Secondary parkinsonism is attributable to a wide variety of causes including supratentorial mass lesions. While tumors are known to present with parkinsonism, chronic subdural hematoma is rarely seen presenting as rapidly deteriorating parkinsonian features with complete disappearance following evacuation of hematoma. The authors present two such patients-70- and 78-year-old males who presented with sudden onset of parkinsonism features. Both failed to recollect any significant head injury. Imaging diagnosed the presence of chronic subdural hematomas, being unilateral in one and bilateral in other. Surgical evacuation resulted in complete resolution of parkinsonian symptoms. These cases reinforce earlier studies for chronic subdural hematoma to be one of the causes of reversible parkinsonism apparently from distortion of basal ganglia mechanically and bringing changes in dopaminergic function, harming the susceptible aging brain.

  7. PATOBIOLOGÍA DEL HEMATOMA SUBDURAL CRÓNICO.

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    Rubén Sabogal Barrios

    2008-01-01

    Full Text Available Treatment of subdural cronic hematoma in all ages is a therapeutic challenge. Chronic subdural hematoma is a disease that can be fatal without surgical treatment. A variety of treatment options like subdural tapping, endoscopic washout, shunting and craniotomy have been discussed. In chronic subdural hematoma, spontaneous resolution with conservative treatment is not an common therapeutic method because it has causes high mortality, requires long periods of time, and finally, many patients need surgical treatment. The etiology, physiopathology and surgical alternatives in the treatment of subdural chronic hematoma is discussed.

  8. An unusual presentation of subdural empyema caused by Porphyromonas gingivalis

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    Ahmed Rasheed

    2013-01-01

    Full Text Available Subdural empyema is an uncommon clinical entity. The first case of Porphyromonas gingivalis subdural empyema is reported. We report a case of 34-year-old male who presented with subdural empyema and sinusitis. Through the utilization of polymerase chain reaction (PCR tests on subdural pus, we were able to confirm the diagnosis and institute appropriate treatment. Early surgical intervention and intravenous antibiotics meant that the patient recovered fully. Infections caused by P. gingivalis should be considered in differential diagnoses of central nervous system (CNS abscesses or subdural empyema especially in patients with precedent periodontal diseases and sinusitis.

  9. Survival in pediatric medulloblastoma: a population-based observational study to improve prognostication.

    Science.gov (United States)

    Weil, Alexander G; Wang, Anthony C; Westwick, Harrison J; Ibrahim, George M; Ariani, Rojine T; Crevier, Louis; Perreault, Sebastien; Davidson, Tom; Tseng, Chi-Hong; Fallah, Aria

    2017-03-01

    Medulloblastoma is the most common form of brain malignancy of childhood. The mainstay of epidemiological data regarding childhood medulloblastoma is derived from case series, hence population-based studies are warranted to improve the accuracy of survival estimates. To utilize a big-data approach to update survival estimates in a contemporary cohort of children with medulloblastoma. We performed a population-based retrospective observational cohort study utilizing the Surveillance, Epidemiology, and End Results Program database that captures all children, less than 20 years of age, between 1973 and 2012 in 18 geographical regions representing 28% of the US population. We included all participants with a presumed or histologically diagnosis of medulloblastoma. The main outcome of interest is survivors at 1, 5 and 10 years following diagnosis. A cohort of 1735 children with a median (interquartile range) age at diagnosis of 7 (4-11) years, with a diagnosis of medulloblastoma were identified. The incidence and prevalence of pediatric medulloblastoma has remained stable over the past 4 decades. There is a critical time point at 1990 when the overall survival has drastically improved. In the contemporary cohort (1990 onwards), the percentage of participants alive was 86, 70 and 63% at 1, 5 and 10 years, respectively. Multivariate Cox-Regression model demonstrated Radiation (HR 0.37; 95% CI 0.30-0.46, p medulloblastoma survival. In contrast to previous reports, the majority of patients survive in the modern era, and those alive 8 years following initial diagnosis are likely a long-term survivor. The importance of minimizing treatment-related toxicity is increasingly apparent given the likelihood of long-term survival.

  10. Craniospinal radiotherapy in adult medulloblastoma

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    Selek, U.; Zorlu, F.; Hurmuz, P.; Cengiz, M.; Gurkaynak, M. [Hacettepe Univ., Ankara (Turkey). Dept. of Radiation Oncology; Turker, A. [Hacettepe Univ., Ankara (Turkey). Dept. of Internal Medicine; Soylemezoglu, F. [Hacettepe Univ., Ankara (Turkey). Dept. of Pathology

    2007-05-15

    Purpose: To evaluate the outcome and prognostic factors of adult patients with medulloblastoma. Patients and Methods: 26 adult medulloblastoma patients with a median age of 27 were subjected to craniospinal radiotherapy. A dose of 30.6 Gy with 1.8 Gy/fraction/day was prescribed to M0 patients, while 36 Gy were to be applied in patients with positive cerebrospinal liquor findings. The posterior fossa was boosted to 54 Gy. While 20 patients underwent external-beam radiotherapy alone, only six received sequential adjuvant chemotherapy. Results: Male/female ratio was 1.2. Preradiotherapy Karnofsky performance status was recorded as median 100%. 50% were classified as poor risk (n = 10, subtotal resection; n = 3, M+). The median follow-up time was 46.5 months. The 5-year actuarial survival rates for recurrence-free, distant metastasis-free, disease-free, and overall survival were 82.5%, 90.8%, 73.5%, and 89.7%, respectively. Patient characteristics, treatment factors and tumor characteristics failed to show any significance in univariate analysis. Grade 3 or 4 late morbidities were not observed. Conclusion: Yet, the current standard of care seems to remain craniospinal irradiation after maximal surgical resection of the primary neoplasm without clear indications for adjuvant chemotherapy. (orig.)

  11. Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma

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    Sara Badodi

    2017-12-01

    Full Text Available Summary: We describe molecular convergence between BMI1 and CHD7 in the initiation of medulloblastoma. Identified in a functional genomic screen in mouse models, a BMI1High;CHD7Low expression signature within medulloblastoma characterizes patients with poor overall survival. We show that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. We provide evidence that repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7. : Badodi et al. find convergence of the chromatin modifiers BMI1 and CHD7 in medulloblastoma pathogenesis, and they show that this pathway regulates tumor proliferation and growth via ERK signaling. Keywords: BMI1, CHD7, DUSP4, ERK, medulloblastoma, PcG genes, mouse models, epigenetics, chromatin

  12. Oncogenic role of cytomegalovirus in medulloblastoma?

    NARCIS (Netherlands)

    Hortal, Alejandro M.; Vermeulen, Jeroen F.; Van Hecke, Wim; Bovenschen, Niels

    2017-01-01

    Medulloblastoma is the most common solid tumor among children. Current therapeutic strategies for this malignancy include surgical resection, radiation therapy and chemotherapy. However, these treatments are accompanied with serious side effects such as neurological complications and psychosocial

  13. Oncogenic role of cytomegalovirus in medulloblastoma?

    Science.gov (United States)

    Hortal, Alejandro M; Vermeulen, Jeroen F; Van Hecke, Wim; Bovenschen, Niels

    2017-11-01

    Medulloblastoma is the most common solid tumor among children. Current therapeutic strategies for this malignancy include surgical resection, radiation therapy and chemotherapy. However, these treatments are accompanied with serious side effects such as neurological complications and psychosocial problems, due to the severity of treatment on the developing nervous system. To solve this problem, novel therapeutic approaches are currently being investigated. One of them is targeting human cytomegalovirus in medulloblastoma cancer cells. However, this approach is still under debate, since the presence of cytomegalovirus in medulloblastomas remains controversial. In this review, we discuss the current controversies on the role of cytomegalovirus in medulloblastoma oncogenesis and the potential of cytomegalovirus as a novel (immuno)therapeutic target. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  14. Genetic and molecular alterations across medulloblastoma subgroups.

    Science.gov (United States)

    Skowron, Patryk; Ramaswamy, Vijay; Taylor, Michael D

    2015-10-01

    Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.

  15. Bilateral Biconvex Frontal Chronic Subdural Hematoma Mimicking ...

    African Journals Online (AJOL)

    involving left upper and lower limb with exaggerated ipsilateral deep tendon reflexes and extensor plantar. ... as a result of indirect signs of a space-occupying lesion are easily recognizable on CT, bilateral CSDH may ... diagnosis and for the management of such lesions. Key words: Chronic subdural hematoma, extradural.

  16. Surgery for chronic subdural hematoma in nonagenarians

    DEFF Research Database (Denmark)

    Bartek, J; Sjåvik, K; Ståhl, F

    2017-01-01

    OBJECTIVE: Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90 years or older. The aim of this study was to investigate outcome after cSDH s...

  17. Subdural Empyema: Clinical Presentations and Management ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... Subdural empyema: Clinical presentations and management options for an uncommon neurosurgical emergency in a developing country. Niger J Clin Pract 2017;20:1221-5. This is an open access article distributed under the terms of the Creative Commons. Attribution-Non Commercial-Share Alike 3.0 ...

  18. High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells.

    Science.gov (United States)

    da Silva, Patrícia Benites Gonçalves; Teixeira Dos Santos, Márcia Cristina; Rodini, Carolina Oliveira; Kaid, Carolini; Pereira, Márcia Cristina Leite; Furukawa, Gabriela; da Cruz, Daniel Sanzio Gimenes; Goldfeder, Mauricio Barbugiani; Rocha, Clarissa Ribeiro Reily; Rosenberg, Carla; Okamoto, Oswaldo Keith

    2017-03-21

    Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer.

  19. Role of MXD3 in proliferation of DAOY human medulloblastoma cells.

    Directory of Open Access Journals (Sweden)

    Gustavo A Barisone

    Full Text Available A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs in which the sonic hedgehog (SHH pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.

  20. Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization.

    Science.gov (United States)

    Bhatia, Shilpa; Baig, Nimrah A; Timofeeva, Olga; Pasquale, Elena B; Hirsch, Kellen; MacDonald, Tobey J; Dritschilo, Anatoly; Lee, Yi Chien; Henkemeyer, Mark; Rood, Brian; Jung, Mira; Wang, Xiao-Jing; Kool, Marcel; Rodriguez, Olga; Albanese, Chris; Karam, Sana D

    2015-04-20

    The expression of members of the Eph family of receptor tyrosine kinases and their ephrin ligands is frequently dysregulated in medulloblastomas. We assessed the expression and functional role of EphB1 in medulloblastoma cell lines and engineered mouse models. mRNA and protein expression profiling showed expression of EphB1 receptor in the human medulloblastoma cell lines DAOY and UW228. EphB1 downregulation reduced cell growth and viability, decreased the expression of important cell cycle regulators, and increased the percentage of cells in G1 phase of the cell cycle. It also modulated the expression of proliferation, and cell survival markers. In addition, EphB1 knockdown in DAOY cells resulted in significant decrease in migration, which correlated with decreased β1-integrin expression and levels of phosphorylated Src. Furthermore, EphB1 knockdown enhanced cellular radiosensitization of medulloblastoma cells in culture and in a genetically engineered mouse medulloblastoma model. Using genetically engineered mouse models, we established that genetic loss of EphB1 resulted in a significant delay in tumor recurrence following irradiation compared to EphB1-expressing control tumors. Taken together, our findings establish that EphB1 plays a key role in medulloblastoma cell growth, viability, migration, and radiation sensitivity, making EphB1 a promising therapeutic target.

  1. Data on the number and frequency of scientific literature citations for established medulloblastoma cell lines

    Directory of Open Access Journals (Sweden)

    D.P. Ivanov

    2016-12-01

    Full Text Available This article collates information about the number of scientific articles mentioning each of the established medulloblastoma cell lines, derived through a systematic search of Web of Science, Scopus and Google Scholar in 2016. The data for each cell line have been presented as raw number of citations, percentage share of the total citations for each search engine and as an average percentage between the three search engines. In order to correct for the time since each cell line has been in use, the raw citation data have also been divided by the number of years since the derivation of each cell line. This is a supporting article for a review of in vitro models of medulloblastoma published in “in vitro models of medulloblastoma: choosing the right tool for the job” (D.P. Ivanov, D.A. Walker, B. Coyle, A.M. Grabowska, 2016 [1].

  2. Role of MYC in Medulloblastoma

    Science.gov (United States)

    Roussel, Martine F.; Robinson, Giles W.

    2013-01-01

    Since its discovery as an oncogene carried by the avian acute leukemia virus MC29 in myelocytomatosis (Roussel et al. 1979) and its cloning (Vennstrom et al. 1982), c-MYC (MYC), as well as its paralogs MYCN and MYCL1, has been shown to play essential roles in cycling progenitor cells born from proliferating zones during embryonic development, and in all proliferating cells after birth. MYC deletion induces cell-cycle exit or cell death, depending on the cell type and milieu, whereas MYC and MYCN amplification or overexpression promotes cell proliferation and occurs in many cancers. Here, we review the relationship of MYC family proteins to the four molecularly distinct medulloblastoma subgroups, discuss the possible roles MYC plays in each of these subgroups and in the developing cells of the posterior fossa, and speculate on possible therapeutic strategies targeting MYC. PMID:24186490

  3. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian

    2012-11-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

  4. Comparison Between Cerebral Tissue Oxygen Tension and Energy Metabolism in Experimental Subdural Hematoma

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Engell, Susanne I; Johnsen, Rikke Aagaard

    2011-01-01

    BACKGROUND: An experimental swine model (n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO(2)) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO...

  5. Hand1 overexpression inhibits medulloblastoma metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Asuthkar, Swapna; Guda, Maheedhara R. [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Martin, Sarah E. [Department of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Antony, Reuben; Fernandez, Karen [Department of Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Lin, Julian [Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Tsung, Andrew J. [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Illinois Neurological Institute, Peoria, IL 61656 (United States); Velpula, Kiran K., E-mail: velpula@uic.edu [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States)

    2016-08-19

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. - Highlights: • Hand1 expression is downregulated in Medulloblastoma. • Hand1 over expression reduce

  6. Association of Antithrombotic Drug Use With Subdural Hematoma Risk

    DEFF Research Database (Denmark)

    Gaist, David; Rodríguez, Luis Alberto García; Hellfritzsch, Maja

    2017-01-01

    Importance: Incidence of subdural hematoma has been reported to be increasing. To what extent this is related to increasing use of antithrombotic drugs is unknown. Objectives: To estimate the association between use of antithrombotic drugs and subdural hematoma risk and determine trends in subdural...... with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. Results: Among 10 010 patients with subdural hematoma (mean age, 69.2 years; 3462 women [34.6%]), 47.3% were taking antithrombotic medications. Current use of low-dose aspirin (cases: 26...... hematoma incidence and antithrombotic drug use in the general population. Design, Setting, and Participants: Case-control study of 10 010 patients aged 20 to 89 years with a first-ever subdural hematoma principal discharge diagnosis from 2000 to 2015 matched by age, sex, and calendar year to 400...

  7. Long non-coding RNA CRNDE promotes tumor growth in medulloblastoma.

    Science.gov (United States)

    Song, H; Han, L-M; Gao, Q; Sun, Y

    2016-06-01

    Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over the past decades, a novel therapeutic strategy is urgently required to increase long-term survival. This study aimed to understand the role of a long non-coding RNA (lncRNA), colorectal neoplasia differentially expressed (CRNDE), in medulloblastoma tumor growth. The transcript level of CRNDE was initially examined in dissected clinical tissues and cultured cancerous cells. Effects of CRNDE knockdown on cell viability and colony formation in vitro were assessed using the CCK-8 and colony formation assays, respectively. Cell cycle progression and survival were also determined after CRNDE knockdown. A xenograft mouse model of human medulloblastoma was established by injecting nude mice with medulloblastoma cells stably depleted of CRNDE expression. Our data suggest that transcript levels of CRNDE are elevated in clinical medulloblastoma tissues instead of in adjacent non-cancerous tissues. Knockdown of CRNDE significantly slowed cell proliferation rates and inhibited colony formation in Daoy and D341 cells. Tumor growth in vivo was also inhibited after CRNDE knockdown. Moreover, after knockdown of CRNDE, cell cycle progression was arrested in S phase and apoptosis was promoted by 15-20% in Daoy and D341 cells. In vivo data further showed that proliferating cell nuclei antigen (PCNA) was decreased, whereas the apoptosis initiator cleaved-caspase-3 was increased upon CRNDE knockdown in cancerous tissues from the mouse model. All these data suggest that CRNDE promotes tumor growth both in vitro and in vivo. This growth-promotion effect might be achieved via arresting cell cycle progression and inhibiting apoptosis. Therapeutics against CRNDE may be a novel strategy for the treatment of medulloblastoma.

  8. Overexpressed TP73 induces apoptosis in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Perlaky Laszlo

    2007-07-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. Methods We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Results Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and

  9. Medulloblastoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  10. Spontaneous acute subdural hematoma in a patient with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Abrar Ahad Wani

    2012-01-01

    Full Text Available Acute spontaneous subdural hematoma in a patient of multiple myeloma receiving chemotherapy is an unknown event, needing an urgent neurosurgical management. We report this patient who presented with progressive neurological deterioration and a low platelet count. She was successfully managed by craniotomy and evacuation of subdural hematoma with intraoperative transfusion of platelets. The acute spontaneous subdural hematoma in her was probably related to the bleeding diathesis due to thrombocytopenia associated with chemotherapy.

  11. Three-dimensional (3D) reconstruction and quantitative analysis of the microvasculature in medulloblastoma and ependymoma subtypes.

    NARCIS (Netherlands)

    Gilhuis, H.J.; Laak, J.A.W.M. van der; Pomp, J.; Kappelle, A.C.; Gijtenbeek, J.M.M.; Wesseling, P.

    2006-01-01

    In the World Health Organisation (WHO) classification of tumours of the nervous system, four main histopathological subtypes of medulloblastomas (classic medulloblastoma, desmoplastic medulloblastoma, medulloblastoma with extensive nodularity and advanced neuronal differentiation and large

  12. PRAME gene expression profile in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Tânia Maria Vulcani-Freitas

    2011-02-01

    Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

  13. In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

    Science.gov (United States)

    Holst, Martin I.; Pietsch, Thorsten; Dilloo, Dagmar

    2014-01-01

    Regardless of the recent advances in cytotoxic therapies, 30% of children diagnosed with medulloblastoma. succumb to the disease. Therefore, novel therapeutic approaches are warranted. Here we demonstrate that Pazopanib a clinically approved multi-kinase angiogenesis inhibitor (MKI) inhibits proliferation and apoptosis in medulloblastoma cell lines. Moreover, Pazopanib profoundly attenuates medulloblastoma cell migration, a prerequisite for tumor invasion and metastasis. In keeping with the observed anti-neoplastic activity of Pazopanib, we also delineate reduced phosphorylation of the STAT3 protein, a key regulator of medulloblastoma proliferation and cell survival. Finally, we document profound in vivo activity of Pazopanib in an orthotopic mouse model of the most aggressive c-myc amplified human medulloblastoma variant. Pazopanib reduced the growth rate of intracranial growing medulloblastoma and significantly prolonged the survival. Furthermore, to put these results into a broader perspective we analysed Pazopanib side by side with the MKI Sorafenib. Both compounds share a similar target profile but display different pharmacodynamics and pharmacokinetics with distinct cytotoxic activity in different tumor entities. Thus, we identified Pazopanib as a new promising candidate for a rational clinical assessment for targeted paediatric medulloblastoma therapy. PMID:25216529

  14. ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy.

    Science.gov (United States)

    Morfouace, Marie; Cheepala, Satish; Jackson, Sadhana; Fukuda, Yu; Patel, Yogesh T; Fatima, Soghra; Kawauchi, Daisuke; Shelat, Anang A; Stewart, Clinton F; Sorrentino, Brian P; Schuetz, John D; Roussel, Martine F

    2015-09-15

    While a small number of plasma membrane ABC transporters can export chemotherapeutic drugs and confer drug resistance, it is unknown whether these transporters are expressed or functional in less therapeutically tractable cancers such as Group 3 (G3) medulloblastoma. Herein we show that among this class of drug transporters, only ABCG2 was expressed at highly increased levels in human G3 medulloblastoma and a mouse model of this disease. In the mouse model, Abcg2 protein was expressed at the plasma membrane where it functioned as expected on the basis of export of prototypical substrates. By screening ABC substrates against mouse G3 medulloblastoma tumorspheres in vitro, we found that Abcg2 inhibition could potentiate responses to the clinically used drug topotecan, producing a more than 9-fold suppression of cell proliferation. Extended studies in vivo in this model confirmed that Abcg2 inhibition was sufficient to enhance antiproliferative responses to topotecan, producing a significant survival advantage compared with subjects treated with topotecan alone. Our findings offer a preclinical proof of concept for blockade of ABCG2 transporter activity as a strategy to empower chemotherapeutic responses in G3 medulloblastoma. ©2015 American Association for Cancer Research.

  15. Targeting human medulloblastoma: oncolytic virotherapy with myxoma virus is enhanced by rapamycin.

    Science.gov (United States)

    Lun, Xue Qing; Zhou, Hongyuan; Alain, Tommy; Sun, Beichen; Wang, Limei; Barrett, John W; Stanford, Marianne M; McFadden, Grant; Bell, John; Senger, Donna L; Forsyth, Peter A

    2007-09-15

    We have shown previously the oncolytic potential of myxoma virus in a murine xenograft model of human glioma. Here, we show that myxoma virus used alone or in combination with rapamycin is effective and safe when used in experimental models of medulloblastoma in vitro and in vivo. Nine of 10 medulloblastoma cell lines tested were susceptible to lethal myxoma virus infection, and pretreatment of cells with rapamycin increased the extent of in vitro oncolysis. Intratumoral injection of live myxoma virus when compared with control inactivated virus prolonged survival in D341 and Daoy orthotopic human medulloblastoma xenograft mouse models [D341 median survival: 21 versus 12.5 days; P = 0.0008; Daoy median survival: not reached (three of five mice apparently "cured" after 223 days) versus 75 days; P = 0.0021]. Rapamycin increased the extent of viral oncolysis, "curing" most Daoy tumor-bearing mice and reducing or eliminating spinal cord and ventricle metastases. Rapamycin enhanced tumor-specific myxoma virus replication in vivo and prolonged survival of D341 tumor-bearing mice (median survival of mice treated with live virus (LV) and rapamycin, versus LV alone, versus rapamycin alone, versus inactivated virus: 25 days versus 19, 13, and 11 days, respectively; P myxoma virus oncolysis. These observations suggest that myxoma virus may be an effective oncolytic agent against medulloblastoma and that combination therapy with signaling inhibitors that modulate activity of the phosphatidylinositol 3-kinase/Akt pathway will further enhance the oncolytic potential of myxoma virus.

  16. A case with Parkinsonism secondary to bilateral subdural hematoma

    Directory of Open Access Journals (Sweden)

    Adalet Arıkanoğlu

    2011-03-01

    Full Text Available Subdural hematoma is a rare cause of secondary Parkinsonism. In this study, we presented a case of Parkinsonian syndrome caused by a bilateral subdural hematoma. The patient’s Parkinsonism completely healed following successful surgical removal of the hematomas without any anti-parkinson drug.

  17. Lumbar Puncture in Brain Abscessor Subdural Empyema: Not an ...

    African Journals Online (AJOL)

    Objective To assess the role of lumbar puncture (LP) in aiding diagnosis and influencing outcome in patients with intracranial brain abscess or subdural empyema. Methods The records of patients admitted with space occupying intracranial infective mass lesions (brain abscess and subdural empyema) to the neurosurgical ...

  18. Management of Chronic Subdural Haematoma in a Case of ...

    African Journals Online (AJOL)

    this case conservative management has also resulted in ... right side. Hemiparesis developed gradually over a period of 20 days which corresponded to slow increase in the size of the chronic subdural haematoma and pressure effect over motor cortex. ... enlargement of chronic subdural haematomas was thought to be due ...

  19. Case report: Calcified chronic subdural haematoma in an elderly ...

    African Journals Online (AJOL)

    Calcified chronic subdural haematoma [CCSDH] is a rare complication of the relatively more common condition of Chronic Subdural Haematoma (CSDH). We present the case of a 68yr old man referred with a 2 week history of sudden onset Right hemi paresis generalized tonic clonic seizures and aphasia. There was a ...

  20. Chronic subdural haematoma: review of 96 cases attending the ...

    African Journals Online (AJOL)

    Background: Chronic subdural haematoma is not uncommon in Africa. Early diagnosis and treatment is satisfying. Simpler operative procedures are generally effective. This review is meant to find out the situation regarding the condition in Ghana. Study design: A retrospective study of patients with chronic subdural ...

  1. Extramedullary Hematopoiesis: An Unusual Finding in Subdural Hematomas

    Directory of Open Access Journals (Sweden)

    Rong Li

    2011-01-01

    Full Text Available We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.

  2. Recurrent subdural hematoma secondary to headbanging: A case report.

    Science.gov (United States)

    Nitta, Naoki; Jito, Junya; Nozaki, Kazuhiko

    2015-01-01

    "Headbanging" is the slang term used to denote violent shaking of one's head in time with the music. This abrupt flexion-extension movement of the head to rock music extremely rarely causes a subdural hematoma. A 24-year-old female was admitted to our department because of right sided partial seizure and acute or subacute subdural hematoma over the left cerebral convexity. She had no history of recent head trauma but performed headbanging at a punk rock concert at 3 days before admission. Since, she had a previous acute subdural hematoma on the same side after an accidental fall from a baby buggy when she was 11 months old, the present was recurrent subdural hematoma probably due to headbanging. Headbanging has the hazardous potential to cause a subdural hematoma.

  3. Dissecting the genomic complexity underlying medulloblastoma

    DEFF Research Database (Denmark)

    Jones, David T W; Jäger, Natalie; Kool, Marcel

    2012-01-01

    Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tum...

  4. Chemotherapy for children with medulloblastoma.

    Science.gov (United States)

    Michiels, Erna M C; Schouten-Van Meeteren, Antoinette Y N; Doz, François; Janssens, Geert O; van Dalen, Elvira C

    2015-01-01

    Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by deleting (craniospinal) RT in very young children and by diminishing the dose and field to the craniospinal axis and reducing the boost volume to the tumour bed in older children. 1. to determine the event-free survival/disease-free survival (EFS/DFS) and overall survival (OS) in children with medulloblastoma receiving chemotherapy as a part of their primary treatment, as compared with children not receiving chemotherapy as part of their primary treatment; 2. to determine EFS/DFS and OS in children with medulloblastoma receiving standard-dose RT without chemotherapy, as compared with children receiving reduced-dose RT with chemotherapy as their primary treatment. to determine possible adverse effects of chemotherapy and RT, including long-term adverse effects and effects on quality of life. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 7), MEDLINE/PubMed (1966 to August 2013) and EMBASE/Ovid (1980 to August 2013). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (August 2013). Randomised controlled trials (RCTs) evaluating the above treatments in children (aged 0 to 21 years) with medulloblastoma. Two review authors independently performed study selection, data extraction and risk of bias assessment. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. Where possible, we pooled results. The search identified seven RCTs, including 1080 children, evaluating treatment including chemotherapy and treatment not including chemotherapy. The meta-analysis of EFS/DFS not including disease progression during therapy as an event in the

  5. Subdural drainage versus subperiosteal drainage in burr-hole trepanation for symptomatic chronic subdural hematomas.

    Science.gov (United States)

    Bellut, David; Woernle, Christoph Michael; Burkhardt, Jan-Karl; Kockro, Ralf Alfons; Bertalanffy, Helmut; Krayenbühl, Niklaus

    2012-01-01

    Symptomatic chronic subdural hematoma (scSDH) is one of the most frequent diseases in neurosurgical practice, and its incidence is increasing. However, treatment modalities are still controversial. The aim of this retrospective single-center study is to compare for the first time two surgical methods in the treatment of subdural hematoma that have been proven to be efficient in previous studies in a direct comparison. We analyzed the data of 143 scSDHs in 113 patients undergoing surgery for subdural hematoma with placement of subperiosteal or subdural drainage after double burr-hole trepanation for hematoma evacuation. Overall, there were no statistically significant differences regarding general patient characteristics, preoperative and postoperative symptoms, postoperative hematoma remnant, rates of recurrences, mortality, complications, and outcome at discharge and at 3-month follow up between the groups. There was a close to significant tendency of lower mortality after placement of subperiosteal drainage system and a tendency towards lower rate of recurrent hematoma after placement of subdural drainage system. Our study shows for the first time a direct comparison of two mainly used surgical techniques in the treatment of scSDH. Both methods proved to be highly effective, and general patient data, complications, outcome and mortality of both groups are equal or superior compared with previously published series. Because there is a clear tendency to less mortality and fewer serious complications, treatment with double burr-hole trepanation, irrigation, and placement of subperiosteal drainage is our treatment of choice in patients with predictable high risk of complications. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. A Rare Complication of Subdural-peritoneal Shunt: Migration of Catheter Components through the Pelvic Inlet into the Subdural Space.

    Science.gov (United States)

    Çakir, Mürteza; Yilmaz, Atilla; Çalikoğlu, Çağatay

    2017-01-01

    Subdural-peritoneal (SP) shunting is a simple procedure to treat subdural hygromas; however, several rare complications such as shunt migration exist. A 15-year-old boy presented with headache, nausea, and vomiting, and underwent SP shunting for left frontoparietal chronic subdural effusion. Six weeks later, radiographic examinations revealed total migration of the shunt through the pelvic inlet. The migrated shunt was replaced with a new SP shunt. Four weeks later, radiographic examinations revealed shunt migration into the subdural space. The shunt catheter was removed and the subdural effusion was evacuated. Shunt migration may result from pressure differences between the abdomen and the cranium or from head movement, and insufficient fixation and/or large burr holes can facilitate shunt migration. Double firm anchoring and small-sized burr holes can prevent this complication. SP shunt is a simple procedure, and its assumed complications can be prevented through precaution.

  7. Neurocritical Care of Acute Subdural Hemorrhage.

    Science.gov (United States)

    Al-Mufti, Fawaz; Mayer, Stephan A

    2017-04-01

    Although urgent surgical hematoma evacuation is necessary for most patients with subdural hematoma (SDH), well-orchestrated, evidenced-based, multidisciplinary, postoperative critical care is essential to achieve the best possible outcome. Acute SDH complicates approximately 11% of mild to moderate traumatic brain injuries (TBIs) that require hospitalization, and approximately 20% of severe TBIs. Acute SDH usually is related to a clear traumatic event, but in some cases can occur spontaneously. Management of SDH in the setting of TBI typically conforms to the Advanced Trauma Life Support protocol with airway taking priority, and management breathing and circulation occurring in parallel rather than sequence. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD

    2015-03-01

    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  9. Acute Spontaneous Posterior Fossa Subdural Hematoma

    Directory of Open Access Journals (Sweden)

    Osama Shukir Muhammed Amin

    2014-02-01

    Full Text Available Acute posterior fossa subdural hematomas are rare and most of them are trauma-related. Non-traumatic ones have been reported in patients who had idiopathic thrombocytopenic purpura or those who had been receiving anticoagulant therapy. We report on the case of 57-year-old Iranian man who developed sudden severe occipital headache, drowsiness, repeated vomiting, and instability of stance and gait. He was neither hypertensive nor diabetic. No history of head trauma was obtained and he denied illicit drug or alcohol ingestion. A preliminary diagnosis of acute intra-cerebellar hemorrhage was made. His CT brain scan revealed an acute right-sided, extra-axial, crescent-shaped hyperdense area at the posterior fossa. His routine blood tests, platelets count, bleeding time, and coagulation profile were unremarkable. The patient had spontaneous acute infratentorial subdural hematoma. He was treated conservatively and discharged home well after 5 days. Since then, we could not follow-up him, clinically and radiologically because he went back to Iran. Our patient’s presentation, clinical course, and imaging study have called for conservative management, as the overall presentation was relatively benign. Unless the diagnosis is entertained and the CT brain scan is well-interpreted, the diagnosis may easily escape detection.

  10. Subdural haematoma in pregnancy-induced idiopathic thrombocytopenia: Conservative management

    Directory of Open Access Journals (Sweden)

    Maitree Pandey

    2010-01-01

    Full Text Available Conservative management of subdural haematoma with antioedema measures in second gravida with idiopathic thrombocytopenic purpura (ITP resulted in resolution of haematoma. We present a case of second gravida with ITP who developed subdural haematoma following normal vaginal delivery. She was put on mechanical ventilation and managed conservatively with platelet transfusion, Mannitol 1g/kg, Dexamethasone 1mg/kg and Glycerol 10ml TDS. She regained consciousness and was extubated after 48 hrs. Repeat CT after 10 days showed no mass effect with resolving haematoma which resolved completely after 15 days. Trial of conservative management is safe in pregnant patient with ITP who develops subdural haematoma.

  11. Chronic calcified subdural empyema occurring 46 years after surgery.

    Science.gov (United States)

    Kaspera, Wojciech; Bierzyńska-Macyszyn, Grazyna; Majchrzak, Henryk

    2005-03-01

    The authors present a case of a 47-year-old female in whom there was diagnosed a chronic calcified subdural empyema 46 years after the removal of an acute subdural empyema resulting from complications after otitis media. The patient had suffered from grand mal convulsions and partial epileptic seizures occurring 3-4 times a month. A large frontotemporoparietal craniotomy was carried out and the subdural empyema filled with numerous brownish-black, uncharacteristic tissue fragments together with the partially calcified and ossified capsule was removed. The empyema mass was found to be sterile for bacteria. After the operation, mental disability symptoms began to withdraw and the number of epileptic seizures decreased.

  12. A case report and technical tip of chronic subdural hematoma treated by the placement of a subdural peritoneal shunt

    Directory of Open Access Journals (Sweden)

    Andres M. Alvarez-Pinzon

    2017-02-01

    Full Text Available Background: Chronic subdural hematomas (CSDH tend to occur most commonly in the elderly population, usually resulting from minor or insignificant head trauma. The pathophysiology behind CSDH is often directly associated with cerebral atrophy, and other causes of cerebral atrophy such as alcoholism or dementia. Other predisposing factors include diabetes, coagulopathy, use of anticoagulants (including aspirin, seizure disorders, and CSF shunts. Considerable evidence supporting the use of external drainage after evacuation of primary CSDH is readily available in the literature. Case report: We report the case of a 72 year-old male with a history of recurrent left subdural hematoma presenting to the neurosurgical clinic with a two-day history of personality changes, difficulty speaking, urinary incontinence, and headaches. Burr hole evacuation was performed with the placement of a subdural peritoneal shunt. At the one-month follow-up appointment, the patient had complete resolution of symptoms and CT scan showed no new recurrence of the subdural hematoma. Conclusions: Although several treatment options are available for the management of CSDH, recurrence of hematoma is a major and very common complication that may result in re-injury due to mass effect caused by chronic hematoma. However, placement of subdural peritoneal shunt for the treatment of CSDH can reduce the recurrence rate of CSDH and therefore, reduce the risk of brain re-injury. Keywords: Chronic subdural hematoma, CSDH, Subdural peritoneal shunt, Head trauma

  13. Metastatic Medulloblastoma in Childhood: Chang's Classification Revisited

    Directory of Open Access Journals (Sweden)

    Christelle Dufour

    2012-01-01

    Patients and Methods. This population-based study concerned 117 newly diagnosed children with disseminated medulloblastoma treated at the Institute Gustave Roussy between 1988 and 2008. Metastatic disease was assessed using the Chang staging system, their form (positive cerebrospinal fluid (CSF, nodular or laminar, and their extension (positive cerebrospinal fluid, local, extensive. All patients received preirradiation chemotherapy. Results. The overall survival did not differ according to Chang M-stage. The 5-year overall survival was 59% in patients with nodular metastases compared to 35% in those with laminar metastases. The 5-year overall survival was 76% in patients without disease at the end of pre-irradiation chemotherapy compared to 34% in those without a complete response (P=0.0008. Conclusions. Radiological characteristics of metastases correlated with survival in patients with medulloblastoma. Complete response to sandwich chemotherapy was a strong predictor of survival.

  14. [Congenital medulloblastoma associated with intracranial arachnoid cyst].

    Science.gov (United States)

    Gelabert González, Miguel; Serramito-García, Ramón; Liñares Paz, Mercedes; Aran-Echabe, Eduardo; García-Allut, Alfredo

    2014-01-01

    Arachnoid cysts are very common lesions in paediatric patients, with treatment depending on their location and symptomatology. They are usually solitary cysts but may be associated with other central nervous system diseases such as tumours and congenital deformities. We describe the case of a neonate diagnosed with an arachnoid cyst of the quadrigeminal cistern treated by endoscopy. After the operation, the child's condition worsened; a CT scan revealed a midline posterior fossa tumour not visible in the preoperative neuroradiological tests. The tumour, a medulloblastoma, was partially removed. Given the child's age and the poor prognosis, oncological treatment was not undertaken. The association between medulloblastoma and arachnoid cyst is very rare, and we could find only one such case in the literature. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  15. [Pediatric medulloblastoma: Retrospective series of 52 patients].

    Science.gov (United States)

    Vigneron, C; Antoni, D; Coca, A; Entz-Werlé, N; Lutz, P; Spiegel, A; Jannier, S; Niederst, C; Jarnet, D; Meyer, P; Kehrli, P; Noël, G

    2016-04-01

    Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols. Copyright © 2016. Published by Elsevier SAS.

  16. Streptococcal Subdural Empyema as a Complication of Varicella

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-01-01

    Full Text Available A 3-month-old male infant who presented with a group A streptococcal subdural empyema on day 5 of a varicella skin rash is reported from the University of British Columbia, Vancouver, BC, Canada.

  17. Spectrophotometry of cerebrospinal fluid in subacute and chronic subdural haematomas

    Science.gov (United States)

    Kjellin, K. G.; Steiner, L.

    1974-01-01

    Spectrophotometric examinations were performed on cerebrospinal and subdural fluids in subacute (five patients) and chronic (20 patients) subdural haematomas, with special reference to the diagnostic aid of CSF spectrophotometry. Spectrophotometric xanthochromia of haemorrhagic origin was found in all CSFs examined, while definite visible xanthochromia was observed in only 28% and the CSF was judged as colourless in 52% of those cases. Characteristic bleeding patterns were found spectrophotometrically in all the 20 CSFs examined within 24 hours after lumbar puncture, haematoma patterns being detected in 90-95% of the cases. In many cases the electrophoretically separated protein fractions of CSF and subdural fluids were spectrophotometrically examined. In conclusion, CSF spectrophotometry is a simple, fast, and extremely sensitive method, which in our opinion should be used routinely in the diagnosis of suspected subdural haematomas, if lumbar puncture is not contraindicated. PMID:4140892

  18. Genes differentially expressed in medulloblastoma and fetal brain

    NARCIS (Netherlands)

    Michiels, E. M.; Oussoren, E.; van Groenigen, M.; Pauws, E.; Bossuyt, P. M.; Voûte, P. A.; Baas, F.

    1999-01-01

    Serial analysis of gene expression (SAGE) was used to identify genes that might be involved in the development or growth of medulloblastoma, a childhood brain tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were determined. The distributions of sequence tags in each

  19. Subdural haemorrhage following endoscopic third ventriculostomy. A rare complication.

    LENUS (Irish Health Repository)

    Kamel, M H

    2012-02-03

    Subdural collections or hematomas are frequently observed after shunt placement [7-9, 13], but rarely after ETV [6]. A review of literature revealed 7 cases [1, 5, 6, 10, 12], of which only 1 was symptomatic [5]. We will discuss the causes, management, and methods of prevention of this complication and we will present a case of symptomatic subdural haematoma, following endoscopic third ventriculostomy for illustration.

  20. Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery.

    Science.gov (United States)

    Schneider, Christian; Ramaswamy, Vijay; Kulkarni, Abhaya V; Rutka, James T; Remke, Marc; Tabori, Uri; Hawkins, Cynthia; Bouffet, Eric; Taylor, Michael D

    2015-03-01

    While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups. Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases. The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality

  1. A medulloblastoma showing an unusually long doubling time: reflection of its singular nature.

    Science.gov (United States)

    Doron, Omer; Zauberman, Jacob; Feldman, Ze'ev

    2016-06-01

    In this paper, we present a case of a 4-year-old male diagnosed with a desmoplastic, SHH-type medulloblastoma. Retrospectively, we discovered that the patient underwent an MRI scan at 21 months for reasons unrelated, revealing a T1-enhanced lesion at the vermis, later recognized as the source of the tumor. This unique case provides us with a glimpse into the natural history of this tumor. Our ability to measure tumor volume at two defined time points, 31 months apart, enabled us to deduce the tumor's doubling time. This is defined as the time of one cell cycle divided by the amount of cycling cells, multiplied by cell loss factor. Potential doubling time (Tpot) and actual doubling time (Td), calculated using the Gompertzian model, are the most clinically relevant with regard to a tumor's response to radiotherapy. Here, we show an actual doubling-time (Td) of 78 days, and an extrapolated tumor diameter at the time of birth of 0.25 mm. These results both support the medulloblastoma's embryonic origin, and indicating a threefold longer actual doubling time when compared to previous studies. Taking into account the reported range of medulloblastoma potential doubling time, we deduced a cell loss factor of between 48.9 and 95.5 %. These percentages fall in line with other malignant tumors. Although limited due to the obvious reliance on only two points in time and using the Gompertzian model to complete the remainder, to the best of our knowledge, this is the longest follow-up period reported for medulloblastoma. We have described how a unique turn of events enabled us to get a glimpse into the in situ development of a medulloblastoma over a 31-month period. Regarded sometimes as an idiosyncratic tumor comprised of an array of molecular changes, the complexity of medulloblastoma is displayed here, by revealing for the first time an actual doubling time three- to fourfold the previously known length.

  2. Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma

    DEFF Research Database (Denmark)

    Brodin, N Patrik; Munck af Rosenschöld, Per Martin; Aznar, Marianne C

    2011-01-01

    The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc(®) (RA)) or spot...

  3. A patient with medulloblastoma in its early developmental stage.

    Science.gov (United States)

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  4. Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique

    DEFF Research Database (Denmark)

    Brodin, N. Patrik; af Rosenschold, Per Munck; Blomstrand, Malin

    2014-01-01

    BackgroundWe investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy.MethodsWe included 17 pediatric medulloblastoma...... patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor...... boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques.ResultsMean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment...

  5. G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

    Science.gov (United States)

    2013-01-01

    Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways

  6. Cerebellar Medulloblastoma in Middle-to-Late Adulthood

    Directory of Open Access Journals (Sweden)

    Majid Aljoghaiman

    2018-01-01

    Full Text Available Medulloblastoma is a malignant brain tumor that is typically seen in children. It is classified as an embryonal tumor, classically located within the posterior fossa. When it involves the fourth ventricle, the patient commonly presents with signs and symptoms of raised intracranial pressure secondary to obstructive hydrocephalus. It is exceedingly rare for Medulloblastoma to occur in middle and late adulthood. In this paper, we present a case of a 51-year-old man who presented with a posterior fossa mass that was diagnosed later as Medulloblastoma.

  7. Medulloblastoma with Excessive Nodularity: Radiographic Features and Pathologic Correlate

    Directory of Open Access Journals (Sweden)

    L. A. Yeh-Nayre

    2012-01-01

    Full Text Available Medulloblastoma with extensive nodularity is a rare subtype of the most common malignant childhood brain tumor and has been associated with more favorable prognosis. The authors report the case of a 10-month-old girl with a posterior fossa tumor of excessive nodularity with decreased diffusivity on diffusion-weighted magnetic resonance imaging sequences and robust grape-like postgadolinium contrast enhancing features. The unique neuroradiographic features were confirmed by histopathology and a diagnosis of medulloblastoma with extensive nodularity was made. This case highlights the importance of recognizing this unique medulloblastoma subtype preoperatively, as the more favorable outcome may preclude less aggressive medical management.

  8. A method for medulloblastoma tumor differentiation based on convolutional neural networks and transfer learning

    Science.gov (United States)

    Cruz-Roa, Angel; Arévalo, John; Judkins, Alexander; Madabhushi, Anant; González, Fabio

    2015-12-01

    Convolutional neural networks (CNN) have been very successful at addressing different computer vision tasks thanks to their ability to learn image representations directly from large amounts of labeled data. Features learned from a dataset can be used to represent images from a different dataset via an approach called transfer learning. In this paper we apply transfer learning to the challenging task of medulloblastoma tumor differentiation. We compare two different CNN models which were previously trained in two different domains (natural and histopathology images). The first CNN is a state-of-the-art approach in computer vision, a large and deep CNN with 16-layers, Visual Geometry Group (VGG) CNN. The second (IBCa-CNN) is a 2-layer CNN trained for invasive breast cancer tumor classification. Both CNNs are used as visual feature extractors of histopathology image regions of anaplastic and non-anaplastic medulloblastoma tumor from digitized whole-slide images. The features from the two models are used, separately, to train a softmax classifier to discriminate between anaplastic and non-anaplastic medulloblastoma image regions. Experimental results show that the transfer learning approach produce competitive results in comparison with the state of the art approaches for IBCa detection. Results also show that features extracted from the IBCa-CNN have better performance in comparison with features extracted from the VGG-CNN. The former obtains 89.8% while the latter obtains 76.6% in terms of average accuracy.

  9. Exploratory analysis of ERCC2 DNA methylation in survival among pediatric medulloblastoma patients.

    Science.gov (United States)

    Banfield, Emilyn; Brown, Austin L; Peckham, Erin C; Rednam, Surya P; Murray, Jeffrey; Okcu, M Fatih; Mitchell, Laura E; Chintagumpala, Murali M; Lau, Ching C; Scheurer, Michael E; Lupo, Philip J

    2016-10-01

    Medulloblastoma is the most frequent malignant pediatric brain tumor. While survival rates have improved due to multimodal treatment including cisplatin-based chemotherapy, there are few prognostic factors for adverse treatment outcomes. Notably, genes involved in the nucleotide excision repair pathway, including ERCC2, have been implicated in cisplatin sensitivity in other cancers. Therefore, this study evaluated the role of ERCC2 DNA methylation profiles on pediatric medulloblastoma survival. The study population included 71 medulloblastoma patients (age DNA methylation profiles were generated from peripheral blood samples using the Illumina Infinium Human Methylation 450 Beadchip. Sixteen ERCC2-associated CpG sites were evaluated in this analysis. Multivariable regression models were used to determine the adjusted association between DNA methylation and survival. Cox regression and Kaplan-Meier curves were used to compare 5-year overall survival between hyper- and hypo-methylation at each CpG site. In total, 12.7% (n=9) of the patient population died within five years of diagnosis. In our population, methylation of the cg02257300 probe (Hazard Ratio=9.33; 95% Confidence Interval: 1.17-74.64) was associated with death (log-rank p=0.01). This association remained suggestive after correcting for multiple comparisons (FDR pDNA methylation within the promoter region of the ERCC2 gene may be associated with survival in pediatric medulloblastoma. If confirmed in future studies, this information may lead to improved risk stratification or promote the development of novel, targeted therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Societal preferences in the treatment of pediatric medulloblastoma: Balancing risk of death and quality of life.

    Science.gov (United States)

    Khakban, Amir; Mohammadi, Tima; Lynd, Larry D; Mabbott, Don; Bouffet, Eric; Gastonguay, Louise; Zafari, Zafar; Malkin, David; Taylor, Michael; Marra, Carlo A

    2017-06-01

    Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence. As such, there is a need to investigate the nature of trade-offs that individuals are willing to make regarding the treatment of medulloblastoma. We used best-worst scaling to estimate the importance of attributes affecting the general public's decision making around the treatment of medulloblastoma. After conducting focus groups, we selected three relevant attributes: (1) the accuracy of the genetic test; (2) the probability of serious adverse effects of the treatment(s); and (3) the survival rate. Using the paired method, we applied a conditional logit model to estimate preferences. In total, 3,006 respondents (51.3% female) with an average age of 43 years answered the questionnaires. All coefficients were statistically significantly different from zero and the attribute levels of adverse effects and the survival rate had the most impact on individuals' stated decision making. Overall, respondents showed high sensitivity to children experiencing disability particularly in the setting of a good prognosis. However, among children with poor prognostic molecular variants, participants showed tolerance about having a child with mild and partial disability compared to a low rate of survival. © 2016 Wiley Periodicals, Inc.

  11. Pharmacological Inhibition of the Protein Kinase MRK/ZAK Radiosensitizes Medulloblastoma.

    Science.gov (United States)

    Markowitz, Daniel; Powell, Caitlin; Tran, Nhan L; Berens, Michael E; Ryken, Timothy C; Vanan, Magimairajan; Rosen, Lisa; He, Mingzu; Sun, Shan; Symons, Marc; Al-Abed, Yousef; Ruggieri, Rosamaria

    2016-08-01

    Medulloblastoma is a cerebellar tumor and the most common pediatric brain malignancy. Radiotherapy is part of the standard care for this tumor, but its effectiveness is accompanied by significant neurocognitive sequelae due to the deleterious effects of radiation on the developing brain. We have previously shown that the protein kinase MRK/ZAK protects tumor cells from radiation-induced cell death by regulating cell-cycle arrest after ionizing radiation. Here, we show that siRNA-mediated MRK depletion sensitizes medulloblastoma primary cells to radiation. We have, therefore, designed and tested a specific small molecule inhibitor of MRK, M443, which binds to MRK in an irreversible fashion and inhibits its activity. We found that M443 strongly radiosensitizes UW228 medulloblastoma cells as well as UI226 patient-derived primary cells, whereas it does not affect the response to radiation of normal brain cells. M443 also inhibits radiation-induced activation of both p38 and Chk2, two proteins that act downstream of MRK and are involved in DNA damage-induced cell-cycle arrest. Importantly, in an animal model of medulloblastoma that employs orthotopic implantation of primary patient-derived UI226 cells in nude mice, M443 in combination with radiation achieved a synergistic increase in survival. We hypothesize that combining radiotherapy with M443 will allow us to lower the radiation dose while maintaining therapeutic efficacy, thereby minimizing radiation-induced side effects. Mol Cancer Ther; 15(8); 1799-808. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.

    Directory of Open Access Journals (Sweden)

    Mai T Dang

    Full Text Available The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.

  13. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.

    Science.gov (United States)

    Dang, Mai T; Wehrli, Suzanne; Dang, Chi V; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.

  14. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

    Science.gov (United States)

    Dang, Mai T.; Wehrli, Suzanne; Dang, Chi V.; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice. PMID:26192445

  15. Reprogramming Medulloblastoma-Propagating Cells by a Combined Antagonism of Sonic Hedgehog and CXCR4.

    Science.gov (United States)

    Ward, Stacey A; Warrington, Nicole M; Taylor, Sara; Kfoury, Najla; Luo, Jingqin; Rubin, Joshua B

    2017-03-15

    The CXCR4 chemokine and Sonic Hedgehog (SHH) morphogen pathways are well-validated therapeutic targets in cancer, including medulloblastoma. However, single-agent treatments with SHH or CXCR4 antagonists have not proven efficacious in clinical trials to date. Here, we discovered that dual inhibition of the SHH and CXCR4 pathways in a murine model of SHH-subtype medulloblastoma exerts potent antitumor effects. This therapeutic synergy resulted in the suppression of tumor-propagating cell function and correlated with increased histone H3 lysine 27 trimethylation within the promoters of stem cell genes, resulting in their decreased expression. These results demonstrate that CXCR4 contributes to the epigenetic regulation of a tumor-propagating cell phenotype. Moreover, they provide a mechanistic rationale to evaluate the combination of SHH and CXCR4 inhibitors in clinical trials for the treatment of medulloblastoma, as well as other cancers driven by SHH that coexpress high levels of CXCR4. Cancer Res; 77(6); 1416-26. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Epidermal Nevus Syndrome Associated with Brain Malformations and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-01-01

    Full Text Available Researchers at Juntendo University and Tokyo Women’s Medical University, Japan; and University of California, San Francisco, Ca, report a male infant with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

  17. Cerebellar Medulloblastoma Metastasis to Sacrum: A Case Report

    Directory of Open Access Journals (Sweden)

    Erdal Kalkan

    2015-12-01

    Full Text Available Introduction: Medulloblastoma is a primitive-neuroectodermal (PNET tumor, mostly localized infratentorially and mostly seen in childhood . It can be seen rarely in adults . Medulloblastoma metastasis is generally seen at bone marrow and bone, such as pelvis, femur, vertebra and costal bones. Case Presentation: A 32-year-old male patient admitted to our clinic with complaints of headache, giddiness, and ataxia. Cystic tumoral lesion was seen in the cerebellum on magnetic resonance imaging (MRI scans. The tumor was excised totally by a paramedian suboccipital craniectomy. Pathological examination results were consistent with medulloblastoma. One year after the operation, the patient was admitted to our clinic with back pain, weakness in his legs and urinary incontinence. A sacral tumor was seen on lumbosacral MRI. Conclusion: This is the first report of a sacral medulloblastoma metastasis case successfully treated with a partial sacrectomy and total tumoral excision. [J Contemp Med 2015; 5(4.000: 261-264

  18. The Neuroradiological Spectra of Adult and Pediatric Medulloblastoma Differ

    DEFF Research Database (Denmark)

    Beier, Dagmar; Kocakaya, Selin; Hau, Peter

    2018-01-01

    PURPOSE: Current knowledge on the spectrum of the neuroradiological appearance of adult medulloblastoma is sparse. Due to the rarity of the disease, adult patients were generally diagnosed and treated similar to children; however, pediatric and adult medulloblastomas display substantial molecular...... for imaging data on single patients. A total of 109 patients were identified and compared to 118 pediatric patients described in 4 cohorts. RESULTS: The average age of the adult patients was 34.3 years. Most adult medulloblastomas (57.6 %) were localized laterally (vs. 14.4 % in pediatric patients). On T1......-weighted sequences, only 41.1 % of all adult medulloblastomas appeared hypointense (vs. 89.3 %) and 69.6 % were hyperintense on T2 sequences (vs. 83 %). In contrast to pediatric patients only 53.3 % showed strong contrast enhancement (pediatric patients 77.1 %), while the contrast uptake of the remainder...

  19. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing

    NARCIS (Netherlands)

    Hovestadt, Volker; Jones, David T. W.; Picelli, Simone; Wang, Wei; Kool, Marcel; Northcott, Paul A.; Sultan, Marc; Stachurski, Katharina; Ryzhova, Marina; Warnatz, Hans-Jörg; Ralser, Meryem; Brun, Sonja; Bunt, Jens; Jäger, Natalie; Kleinheinz, Kortine; Erkek, Serap; Weber, Ursula D.; Bartholomae, Cynthia C.; von Kalle, Christof; Lawerenz, Chris; Eils, Jürgen; Koster, Jan; Versteeg, Rogier; Milde, Till; Witt, Olaf; Schmidt, Sabine; Wolf, Stephan; Pietsch, Torsten; Rutkowski, Stefan; Scheurlen, Wolfram; Taylor, Michael D.; Brors, Benedikt; Felsberg, Jörg; Reifenberger, Guido; Borkhardt, Arndt; Lehrach, Hans; Wechsler-Reya, Robert J.; Eils, Roland; Yaspo, Marie-Laure; Landgraf, Pablo; Korshunov, Andrey; Zapatka, Marc; Radlwimmer, Bernhard; Pfister, Stefan M.; Lichter, Peter

    2014-01-01

    Epigenetic alterations, that is, disruption of DNA methylation and chromatin architecture, are now acknowledged as a universal feature of tumorigenesis. Medulloblastoma, a clinically challenging, malignant childhood brain tumour, is no exception. Despite much progress from recent genomics studies,

  20. Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice

    National Research Council Canada - National Science Library

    Williams, Scott E; Garcia, Idoia; Crowther, Andrew J; Li, Shiyi; Stewart, Alyssa; Liu, Hedi; Lough, Kendall J; O'Neill, Sean; Veleta, Katherine; Oyarzabal, Esteban A; Merrill, Joseph R; Shih, Yen-Yu Ian; Gershon, Timothy R

    2015-01-01

    .... Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor...

  1. Review of the Management of Infected Subdural Hematoma.

    Science.gov (United States)

    Dabdoub, Carlos B; Adorno, Juan Oscar; Urbano, Jair; Silveira, Elisabeth N; Orlandi, Bianca Maria M

    2016-03-01

    Infection of a subdural hematoma is an unusual cause of subdural empyema, with fewer than 50 cases reported in the literature. The appropriate surgical option for this entity has not been determined because of its rarity. We present a case report of a post-traumatic subdural hematoma infected with Escherichia coli that was successfully treated with craniotomy. In addition, we performed a PubMed search to comprehensively illustrate the causative organism, source of infection, clinical picture, surgical treatment, and outcome for this condition. This article presents an update on the condition. A 55-year-old man was admitted to our hospital complaining of headache, seizure, and urinary incontinence. He had a history of alcoholism and several hospitalizations for mild head trauma. Neuroimaging studies revealed a chronic hematic collection in the left frontal-parietal region. Laboratory tests showed increased C-reactive protein levels. In addition, surgical results revealed an infected subdural hematoma. A bacterial culture of the purulent specimen identified E. coli. In view of the urinary complaint and leukocyturia, the cause of the infected subdural hematoma was postulated as a urinary tract infection. Infected subdural hematoma is an unusual disorder. We must keep in mind the possibility of this complication when seeing a patient who presents with any of the 3 most common symptoms in this review. In these patients, craniotomy should be the method of surgical drainage, especially in adults. It ensures maximal drainage of the loculated pus and allows the total removal of the infected hematoma capsule. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Sakruma Metastaz Yapmış Medulloblastoma: Bir Olgu Sunumu

    OpenAIRE

    Kalkan, Erdal; İlik, Mustafa; Keskin, Fatih; Kaya, Bülent

    2018-01-01

    Introduction: Medulloblastoma is a primitive-neuroectodermal (PNET) tumor, mostly localized infratentorially and mostly seen in childhood . It can be seen rarely in adults . Medulloblastoma metastasis is generally seen at bone marrow and bone, such as pelvis, femur, vertebra and costal bones. Case Presentation: A 32-year-old male patient admitted to our clinic with complaints of headache, giddiness, and ataxia. Cystic tumoral lesion was seen in the cerebellum on magnetic resonance imagin...

  3. Cerebellar Medulloblastoma in Middle-to-Late Adulthood

    OpenAIRE

    Aljoghaiman, Majid; Taha, Mahmoud S.; Abdulkader, Marwah M.

    2018-01-01

    Medulloblastoma is a malignant brain tumor that is typically seen in children. It is classified as an embryonal tumor, classically located within the posterior fossa. When it involves the fourth ventricle, the patient commonly presents with signs and symptoms of raised intracranial pressure secondary to obstructive hydrocephalus. It is exceedingly rare for Medulloblastoma to occur in middle and late adulthood. In this paper, we present a case of a 51-year-old man who presented with a posterio...

  4. Spontaneous chronic spinal subdural hematoma associated with spinal arachnoiditis and syringomyelia.

    Science.gov (United States)

    Siddiqi, F; Hammond, R; Lee, D; Duggal, N

    2005-11-01

    Spontaneous chronic spinal subdural hematoma is rare. We describe a case of spontaneous chronic spinal subdural hematoma associated with arachnoiditis and syringomyelia in a 76-year old woman who presented with a 14-year history of progressive myelopathy. MRI scan revealed a thoraco-lumbar subdural cystic lesion and a thoracic syrinx. The patient underwent thoracic laminectomy and decompression of the lesion, which was a subdural hematoma. A myelotomy was performed to drain the syrinx. Pathological examination revealed features consistent with chronic subdural membrane. This report attempts to elucidate the pathogenesis of chronic spinal subdural hematoma. We discuss possible etiological factors in light of the current literature and pathogenesis of both spinal subdural hematoma and syrinx formation.

  5. Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans

    NARCIS (Netherlands)

    Pöschl, J.; Lorenz, A.; Hartmann, W.; von Bueren, A. O.; Kool, M.; Li, S.; Peraud, A.; Tonn, J.-C.; Herms, J.; Xiang, M.; Rutkowski, S.; Kretzschmar, H. A.; Schüller, U.

    2011-01-01

    Medulloblastoma is the most common malignant brain tumor in childhood, and development of targeted therapies is highly desired. Although the molecular mechanisms of malignant transformation are not fully understood, it is known that medulloblastomas may arise from cerebellar granule neuron

  6. The Nelaton Catheter Guard for Safe and Effective Placement of Subdural Drain for Two-Burr-Hole Trephination in Chronic Subdural Hematoma: A Technical Note.

    Science.gov (United States)

    Fichtner, Jens; Beck, Jürgen; Raabe, A; Stieglitz, Lennart Henning

    2015-09-01

    For chronic subdural hematoma, placement of a Blake drain with a two-burr-hole craniotomy is often preferred. However, the placement of such drains carries the risk of penetrating the brain surface or damaging superficial venous structures. To describe the use of a Nelaton catheter for the placement of a subdural drain in two-burr-hole trephination for chronic subdural hematoma. A Nelaton catheter was used to guide placement of a Blake drain into the subdural hematoma cavity and provide irrigation of the hematoma cavity. With the two-burr-hole method, the Nelaton catheter could be removed easily via the frontal burr hole after the Blake drain was in place. We used the Nelaton catheters in many surgical procedures and found it a safe and easy technique. This method allows the surgeon to safely direct the catheter into the correct position in the subdural space. This tool has two advantages. First, the use of a small and flexible Nelaton catheter is a safe method for irrigation of a chronic subdural hematoma cavity. Second, in comparison with insertion of subdural drainage alone through a burr hole, the placement of the Nelaton catheter in subdural space is easier and the risk of damaging relevant structures such as cortical tissue or bridging veins is lower. Thus this technique may help to avoid complications when placing a subdural drain. Georg Thieme Verlag KG Stuttgart · New York.

  7. Probable Opitz trigonocephaly C syndrome with medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Omran, H.; Hildebrandt, F.; Brandis, M. [Freiburg Univ. (Germany)] [and others

    1997-04-14

    We report on a patient with trigonocephaly, biparietal widening as a result of metopic synostosis, strabismus, upslanted palpebral fissures, apparently low-set ears with abnormal helices, deeply furrowed palate, postaxial polysyndactyly of the feet, ankle flexion deformities, cryptorchidism, loose skin, and severe mental retardation, findings compatible with a diagnosis of the Opitz trigonocephaly C syndrome (OTS). At the age of 12 years this patient presented with symptoms of raised intracranial pressure. A biopsy showed findings diagnostic of a medulloblastoma WHO Grade IV, an unprecedented finding in OTS. The possibility of coincidence should not prevent continued surveillance of OTS patients in the future for the occurrence of malignancy. 33 refs., 4 figs., 1 tab.

  8. OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells

    NARCIS (Netherlands)

    Bunt, Jens; Hasselt, Nancy E.; Zwijnenburg, Danny A.; Hamdi, Mohamed; Koster, Jan; Versteeg, Rogier; Kool, Marcel

    2012-01-01

    The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. To study the role OTX2 has in medulloblastoma we investigated the

  9. File list: InP.Neu.05.AllAg.Medulloblastoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Oth.Neu.05.AllAg.Medulloblastoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. Chronic subdural haematoma: Review of 96 cases attending the ...

    African Journals Online (AJOL)

    H :iwevcr late diagnosis can be fatal'. The accumulation of blood in the subdural space is usually due to tearing of bric ging veins. Little force is required to tear these veins and the initial injury may be trivial. Blood accumulation can also be due to cerebr. ll laceration principally at the temporal poles or due to arterial rupturez.

  4. Spontaneous spinal subdural hematoma in a geriatric patient under ...

    African Journals Online (AJOL)

    Spinal subdural haematoma is rare and may be associated with blood dyscrasia, anticoagulant therapy, lumbar puncture, rupture of arteriovenous malformation, tumour bleeding and spinal trauma. We present a 65-year-old female with history of hypertension and atrial fibrillation. She was on anticoagulant. She presented ...

  5. Coexistent Intracerebral and Subdural Hemorrhage : A case Report

    Directory of Open Access Journals (Sweden)

    Khati C

    1999-01-01

    Full Text Available Subdural and Intracerebral Hemorrhage, occuring simultaneously in a patient is a very rare condition. The few case reports found in literature occurred in situations of trauma, coagulopathy, CNS malignancy and in dialysis dependant patients. We report one such case where both conditions coexisted, in the background of poorly controlled hypertension. The possible pathogenesis in this case is discussed.

  6. Hematoma subdural crónico

    Directory of Open Access Journals (Sweden)

    Jairo Martínez Rozo

    1981-07-01

    Full Text Available Se estudiaron 169 pacientes con diagnóstico de Hematoma Subdural Crónico (H.S.C. admitidos en el Servicio Neurocirugía del Hospital San Juan de Dios desde 1959 a 1980. Los datos clínicos y paraclínicos fueron recopilados en un formato precodificado y luego perforados en tarjetas de computador. Usando el Computador 360/40 disponible en el Centro de Cálculo de la Universidad Nacional y el Computador Intel de el DANE y utilizando el programa SPSS se clasificó, ordenó y depuró.la información. Se analizaron en cuadro y gráficas los resultados que son los siguientes: el 75% de los pacientes hospitalizados por T.C.E. tenían Hematomas Subdurales Crónicos. El mayor número de casos estaba entre 50 y 60 años. La incidencia de H.S.C. era más elevada en el grupo de los hombres. La cefalea ocurrió en el 75% de los casos, el antecedente traumático estaba presente en 83% de casos y la alteración de la conciencia en el 71%. El 90% de los pacientes consultó dentro de los primeros 4 meses. La angiografía continúa siendo el examen de elección con el 100% de positividad. En la T.A.C.la isodensidad en diferentes etapas de evolución del H.S.C. dificulta el diagnóstico. El E.E.G. tiene una positividad del 93% . La frecuencia de H.S.C. bilateral fue de 20%. La anisocoria fue un índice poco confiable para indicar el sitio del Hematoma porque hubo 11 casos de anisocoria por midriasis derecha que tenían el hematoma contralateral. El predominio parietal en la localización del H.S,C. creemos que se deba a su mecanismo de producción. Se analiza la mortalidad que fue en el estudio de 8% , las secuelas aumentaron con la edad de los pacientes. El estudio de seguimiento se hizo en el 40% de los pacientes que sobrevivieron y demostró la baja morbilidad del H.S.C.

  7. MiR-206, a Cerebellum Enriched miRNA Is Downregulated in All Medulloblastoma Subgroups and Its Overexpression Is Necessary for Growth Inhibition of Medulloblastoma Cells.

    Science.gov (United States)

    Panwalkar, Pooja; Moiyadi, Aliasgar; Goel, Atul; Shetty, Prakash; Goel, Naina; Sridhar, Epari; Shirsat, Neelam

    2015-07-01

    Medulloblastoma is the most common and a highly malignant pediatric brain tumor located in the cerebellar region of the brain. Medulloblastomas have recently been shown to consist of four distinct molecular subgroups, viz., WNT, SHH, group 3, and group 4. MiR-206, a miRNA first identified as a myomiR due to its enriched expression in skeletal muscle was found to be expressed specifically in the cerebellum, the site of medulloblastoma occurrence. MiR-206 expression was found to be downregulated in medulloblastomas belonging to all the four molecular subgroups as well as in established medulloblastoma cell lines. Further, the expression of murine homolog of miR-206 was also found to be downregulated in SHH subgroup medulloblastomas from the Smo (+/+) transgenic mice and the Ptch1 (+/-) knockout mice. MiR-206 downregulation in all the four medulloblastoma subgroups suggests tumor-suppressive role for miR-206 in medulloblastoma pathogenesis. The effect of miR-206 expression was analyzed in three established medulloblastoma cell lines, viz., Daoy, D425, and D283 belonging to distinct molecular subgroups. Restoration of miR-206 expression to the levels comparable to those in the normal cerebellum, however, was found to be insufficient to inhibit the growth of established medulloblastoma cell lines. OTX2, an oncogenic miR-206 target, overexpressed in all non-SHH medulloblastomas, is known to inhibit myogenic differentiation of medulloblastoma cells. Overexpression of miR-206 was necessary to downregulate OTX2 expression and inhibit growth of medulloblastoma cell lines.

  8. Management of acute subdural hematomas in infants: intrathecal infusion streptokinase for clot lysis combined with subdural to subgaleal shunt.

    Science.gov (United States)

    Larionov, Sergey N; Sorokovikov, Vladimir A; Novozilov, Vladimir A

    2008-04-01

    Subdural hematomas (SDHs) in full-term infants have the potential to cause death or lifelong disability. We report management and outcomes of eight cases of newborn with large SDH treated by streptokinase (SK) lavage and drainage. Between 2003 and 2006, eight infants with large acute SDH with focal or diffuse hypodensity showing signs and symptoms of neurological deterioration were treated by drainage and subdural SK lavage. There were eight full-term infants, five boys and three girls, with ages between 10 days and 2 months. Head injuries were shaken baby syndrome in three cases, fall from height in three cases, caused by traffic accident in one case, and reportedly not due to trauma in one case. In all patients, SDHs were unilateral. We used a new surgical approach, SDH evacuation, involving the subdural instillation of SK for lysis and after drainage of acute SDH in infants. Follow-up in the series ranged from 1 to 42 months (average 30 months). There was no mortality in this series, neither in the early postoperative period nor in the follow-up period. Five patients of this series lead a normal life; two children were mildly neurodevelopmentally delayed. Subdural infusion of SK followed by drainage may be as safe and effective for treatment of acute SDHs in infants as other reported methods.

  9. Predictors of Functional Outcome After Subdural Hematoma: A Prospective Study.

    Science.gov (United States)

    Weimer, Jonathan M; Gordon, Errol; Frontera, Jennifer A

    2017-02-01

    Although the incidence of subdural hematoma (SDH) has increased in the US in the last decade, limited prospective data exist examining risk factors for poor outcome. A prospective, observational study of consecutive SDH patients was conducted from 7/2008 to 11/2011. Baseline clinical data, hospital and surgical course, complications, and imaging data were compared between those with good versus poor 3-month outcomes (modified Rankin Scores [mRS] 0-3 vs. 4-6). A multivariable logistic regression model was constructed to identify independent predictors of poor outcome. 116 SDH patients (18 acute, 56 mixed acute/subacute/chronic, 42 subacute/chronic) were included. At 3 months, 61 (53 %) patients had good outcomes (mRS 0-3) while 55 (47 %) were severely disabled or dead (mRS 4-6). Of those who underwent surgical evacuation, 54/94 (57 %) had good outcomes compared to 7/22 (32 %) who did not (p = 0.030). Patients with mixed acuity or subacute/chronic SDH had significantly better 3-month mRS with surgery (median mRS 1 versus 5 without surgery, p = 0.002) compared to those with only acute SDH (p = 0.494). In multivariable analysis, premorbid mRS, age, admission Glasgow Coma Score, history of smoking, and fever were independent predictors of poor 3-month outcome (all p SDH evacuation tended to improve outcomes (adjusted OR 3.90, 95 % CI 0.96-18.9, p = 0.057). Nearly 50 % of SDH patients were dead or moderate-severely disabled at 3 months. Older age, poor baseline, poor admission neurological status, history of smoking, and fever during hospitalization predicted poor outcomes, while surgical evacuation was associated with improved outcomes among those with mixed acuity or chronic/subacute SDH.

  10. A prospective randomised study to compare the utility and outcomes of subdural and subperiosteal drains for the treatment of chronic subdural haematoma.

    LENUS (Irish Health Repository)

    Kaliaperumal, Chandrasekaran

    2012-11-01

    The usage of a drain following evacuation of a chronic subdural haematoma (CSDH) is known to reduce recurrence. In this study we aim to compare the clinical outcomes and recurrence rate of utilising two different types of drains (subperiosteal and subdural drain) following drainage of a CSDH.

  11. Coregistration of digital photography of the human cortex and cranial magnetic resonance imaging for visualization of subdural electrodes in epilepsy surgery.

    Science.gov (United States)

    Mahvash, Mehran; König, Roy; Wellmer, Jörg; Urbach, Horst; Meyer, Bernhard; Schaller, Karl

    2007-11-01

    To develop a method for the coregistration of digital photographs of the human cortex with head magnetic resonance imaging (MRI) scans for invasive diagnostics and resective neocortical epilepsy surgery. Six chronically epileptic patients (two women, four men; mean age, 34 yr; age range, 20-43 yr) underwent preoperative three-dimensional (3D) T1-weighted MRI scans. Digital photographs of the exposed cortex were taken during implantation of subdural grid electrodes. Rendering software (Analyze 3.1; Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) was used to create an MRI-based 3D model of the brain surface. Digital photographs were manually coregistered with the brain surface MRI model using the registration tool in the Analyze software. By matching the digital photograph and the brain surface model, the position of the subdural electrodes was integrated into the coordinate system of the preoperatively acquired 3D MRI dataset. In all patients, the position of the labeled electrode contacts in relation to the cortical anatomy could be visualized on the 3D models of the cortical surface. At the time of resection, the resulting image of the coregistration process provides a realistic view of the cortex and the position of the subdural electrode. The coregistration of digital photographs of the brain cortex with the results of 3D MRI data sets is possible. This allows for identification of anatomic details underlying the subdural grid electrodes and enhances the orientation of the surgeon.

  12. Diffuse postoperative cerebellar swelling in medulloblastoma: report of two cases.

    Science.gov (United States)

    Ogiwara, Hideki; Dipatri, Arthur J; Bowman, Robin M; Tomita, Tadanori; Alden, Tord D

    2011-05-01

    We report two cases of diffuse cerebellar swelling with upward transtentorial herniation following medulloblastoma resection. We present our insight for managing medulloblastoma with aggressive clinical behavior. Case 1 is a 32-month-old boy. Magnetic resonance imaging (MRI) revealed fourth ventricular mass with diffuse leptomeningeal metastasis. He underwent gross total resectioning of the tumor and histopathology revealed a large cell medulloblastoma. A ventriculoperitoneal shunt was placed on the 25th postoperative day. Ten days after he developed lethargy, and MRI showed diffuse cerebellar swelling with upward herniation. He underwent emergent posterior fossa decompression; however, he remained unresponsive since then. Case 2 is a 31-month-old boy. MRI revealed a fourth ventricular mass with diffuse leptomeningeal metastasis. He underwent gross total resection and histopathology was a large cell medulloblastoma. Due to developing ventriculomegaly, extraventricular drainage was reinserted on the 11th postoperative day. Four days after, he developed lethargy and decerebrate posturing. MRI showed diffuse cerebellar swelling with upward herniation. He underwent aggressive posterior fossa decompression. Chemotherapy was started postoperatively. Gradually, his movement of extremities improved. On the 79th postoperative day, he started to follow commands and talk some words. He was discharged to a rehabilitation institute and has continued to improve since then. Diffuse cerebellar swelling with upward herniation could occur in patients with aggressive medulloblastoma postoperatively. Our patients had diffuse leptomeningeal dissemination of the tumor at the initial presentation. Close monitoring and prompt diagnosis with earlier surgical posterior fossa decompression and administration of chemotherapy may prevent irreversible neurologic deterioration.

  13. The whole-genome landscape of medulloblastoma subtypes.

    Science.gov (United States)

    Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

    2017-07-19

    Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

  14. High expression of DNA methyltransferases in primary human medulloblastoma.

    Science.gov (United States)

    Pócza, T; Krenács, T; Turányi, E; Csáthy, J; Jakab, Z; Hauser, P

    2016-01-01

    Epigenetic alterations have been implicated in cancer development. DNA methylation modulates gene expression, which is catalyzed by DNA methyltransferases (DNMTs). The objective of our study was to evaluate expression of DNMTs in medulloblastoma and analyze its correlation with clinical features. Nuclear expression of DNMT1, DNMT3A and DNMT3B was analyzed in human primary medulloblastoma of 44 patients using immunohistochemistry. Correlation of expression of DNMT levels with classical histological subtypes, novel molecular subgroups and survival of patients was analyzed. Elevated expression of DNMT1, DNMT3A and DNMT3B was observed in 63.64%, 68.18% and 72.73% of all cases, respectively. None of them showed a correlation with classical histology or survival. Concerning molecular subtypes, significantly higher expression of DNMT1 was observed in the SHH group compared to non-SHH samples (p = 0.02), but without significant difference in DNMT3A or DNMT3B levels between any subtypes. In conclusion, DNMT1, DNMT3A and DNMT3B are highly expressed in human medulloblastoma samples, suggesting that promoter hypermethylation may play a role in medulloblastoma development. Demethylation of tumor suppressor gene promoters may be considered as a possible future target in therapy of medulloblastoma.

  15. MPS1 kinase as a potential therapeutic target in medulloblastoma.

    Science.gov (United States)

    Alimova, Irina; Ng, June; Harris, Peter; Birks, Diane; Donson, Andrew; Taylor, Michael D; Foreman, Nicholas K; Venkataraman, Sujatha; Vibhakar, Rajeev

    2016-11-01

    Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma.

  16. Ganglioglioma Arising From Desmoplastic Medulloblastoma: A Case Report and Review of Literature.

    Science.gov (United States)

    Valvi, Santosh; Ziegler, David S

    2017-03-01

    We describe a case of medulloblastoma maturating into ganglioglioma during therapy. A 10-month-old boy was diagnosed with a desmoplastic medulloblastoma and was treated with gross total resection followed by induction chemotherapy. A recurrence in the tumor bed during therapy was managed with focal radiation therapy and consolidation chemotherapy. After further progression, the recurrent tumor was resected completely. The histopathology revealed a benign ganglioglioma with no residual medulloblastoma. This case raises the possibility that a malignant medulloblastoma can differentiate into a benign tumor and suggests that differentiation therapy may have value in the treatment of medulloblastoma. Copyright © 2017 by the American Academy of Pediatrics.

  17. Use of Subdural Evacuating Port System Following Open Craniotomy with Excision of Native Dura and Membranes for Management of Chronic Subdural Hematoma.

    Science.gov (United States)

    Cage, Tene; Bach, Ashley; McDermott, Michael W

    2017-04-26

    An 86-year-old woman was admitted to the intensive care unit with a chronic subdural hematoma (CSDH) and rapid onset of worsening neurological symptoms. She was taken to the operating room for a mini-craniotomy for evacuation of the CSDH including excision of the dura and CSDH membrane. Postoperatively, a subdural evacuation port system (SEPS) was integrated into the craniotomy site and left in place rather than a traditional subdural catheter drain to evacuate the subdural space postoperatively. The patient had a good recovery and improvement of symptoms after evacuation and remained clinically well after the SEPS was removed. We offer the technique of dura and CSDH membrane excision plus SEPS drain as an effective postoperative alternative to the standard craniotomy leaving the native dura intact with traditional subdural drain that overlies the cortical surface of the brain in treating patients with CSDH.

  18. Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma.

    Science.gov (United States)

    Faria, Claudia C; Agnihotri, Sameer; Mack, Stephen C; Golbourn, Brian J; Diaz, Roberto J; Olsen, Samantha; Bryant, Melissa; Bebenek, Matthew; Wang, Xin; Bertrand, Kelsey C; Kushida, Michelle; Head, Renee; Clark, Ian; Dirks, Peter; Smith, Christian A; Taylor, Michael D; Rutka, James T

    2015-08-28

    Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.

  19. Executive function in paediatric medulloblastoma: The role of cerebrocerebellar connections.

    Science.gov (United States)

    Law, Nicole; Smith, Mary Lou; Greenberg, Mark; Bouffet, Eric; Taylor, Michael D; Laughlin, Suzanne; Malkin, David; Liu, Fang; Moxon-Emre, Iska; Scantlebury, Nadia; Mabbott, Donald

    2017-06-01

    Executive functions (EFs) are involved in the attainment, maintenance, and integration of information; these functions may play a key role in cognitive and behavioural outcomes in children treated for medulloblastoma (MB). At present, it remains unclear which EFs are most sensitive to the treatment effects for MB and whether damage to cerebrocerebellar circuitry is associated with EF. We completed a comprehensive evaluation of EF in 24 children treated for MB and 20 age-matched healthy children (HC) and distilled these measures into components. Six components (C1-C6) were extracted from our model, reflecting dissociable constructs of EF: C1 = cognitive efficiency; C2 = planning/problem-solving; C3 = positive cognitive emotion regulation; C4 = working memory; C5 = negative cognitive emotion regulation; and C6 = mixed cognitive emotion regulation. Group differences were found for C1, C2, C3, and C4; the MB group showed poorer performance on EF tasks and made less use of positive cognitive emotion regulation strategies relative to HC. Compromise to cerebrocerebellar microstructure - cerebro-ponto-cerebellar and cerebello-thalamo-cerebral pathways - was evident in children treated for MB compared to HC. We found that cerebrocerebellar circuitry has a mediating effect on one component of EF following treatment for MB - working memory. © 2015 The British Psychological Society.

  20. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

    Science.gov (United States)

    Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

    2016-02-01

    Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

  1. Evasion of Cell Senescence Leads to Medulloblastoma Progression

    Directory of Open Access Journals (Sweden)

    Lukas Tamayo-Orrego

    2016-03-01

    Full Text Available How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1+/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors.

  2. Adult cerebellar medulloblastoma: CT and MRI findings in eight cases

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho Neto, Arnolfo de; Bertoldi, Guilherme A. [Parana Univ., Curitiba, PR (Brazil). Radiologia Diagnostica]. E-mail: arnolfo.carvalho@avalon.sul.com.br; Gasparetto, Emerson L. [Parana Univ., Curitiba, PR (Brazil). Hospital das Clinicas. Secao de Radiologia Diagnostica; Ono, Sergio E. [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina; Gomes, Andre F. [Diagnostico Avancado Por Imagem (DAPI), Curitiba, PR (Brazil)

    2003-06-01

    Medulloblastoma is a brain tumor of neuro epithelial origin, which represents 15 to 30% of all pediatric brain tumors, and less than 1% of CNS adult neoplasms. We report the imaging findings of 8 adult patients with medulloblastoma. The mean age was 35 years, ranging from 20 to 65 years, and the male:female rate was 3:5. The tumors were predominantly lateral (63%), hyperdense on CT scans (83%), and on the MRI, hypointense on T1 (100%) and hyperintense on T2 (80%) weighted images. It was seen intratumoral necrosis and cysts in six cases and calcifications in three. Hydrocephalus was observed in 5 cases and brain stem invasion in four. The imaging findings of medulloblastomas in adults are different of those in child, and also nonspecific. Although these tumors are uncommon in adults, they must be considered in the differential diagnosis of cerebellar masses in the posterior fossa of this age group. (author)

  3. Adult cerebellar medulloblastoma: CT and MRI findings in eight cases

    Directory of Open Access Journals (Sweden)

    Carvalho Neto Arnolfo de

    2003-01-01

    Full Text Available Medulloblastoma is a brain tumor of neuroepithelial origin, which represents 15 to 30% of all pediatric brain tumors, and less than 1% of CNS adult neoplasms. We report the imaging findings of 8 adult patients with medulloblastoma. The mean age was 35 years, ranging from 20 to 65 years, and the male:female rate was 3:5. The tumors were predominantly lateral (63%, hyperdense on CT scans (83%, and on the MRI, hypointense on T1 (100% and hyperintense on T2 (80% weighted images. It was seen intratumoral necrosis and cysts in six cases and calcifications in three. Hydrocephalus was observed in 5 cases and brain stem invasion in four. The imaging findings of medulloblastomas in adults are different of those in child, and also nonspecific. Although these tumors are uncommon in adults, they must be considered in the differential diagnosis of cerebellar masses in the posterior fossa of this age group.

  4. Traumatic acute posterior fossa subdural hematoma – A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Jaiswal Manish

    2014-12-01

    Full Text Available Traumatic subdural hematomas of the posterior fossa are rare but dangerous neurosurgical emergencies that require prompt diagnosis and management to avoid the uniformly poor outcome. We present a case of a teenager with severe TBI and acute subdural hematoma of the posterior fossa that deteriorated rapidly before surgery but eventually made a good recovery. We also the review the literature concerning traumatic posterior fossa subdural hematomas [PFSDH].

  5. Metastasis-associated gene 1 expression in human medulloblastoma and its association with invasion and metastasis in medulloblastoma Daoy cell lines.

    Science.gov (United States)

    Chen, Y S; Li, S P; Xiao, H; Xie, Z Y; Tan, M X; Liu, B; Zhang, W M

    2016-06-17

    This study aims to investigate the expression of metastasis-associated gene 1 (MTA1) in human medulloblastoma, and its significance in the invasion and metastasis in a medulloblastoma cell line. Positive expression rate of MTA1 protein in medulloblastoma and adjacent normal tissues collected from 29 medulloblastoma patients was detected by immunohistochemistry assay in vivo. In in vitro experiments, Daoy cells were transfected with MTA1-targeted small interfering RNA (siRNA, MTA1-siRNA group), niRNA (MTA1-niRNA group), and plasmid vectors (control group). Transfection efficiency was evaluated by PT-PCR and western blot; cell adhesion, migration, and invasion capacity was assessed by adhesion assays, scratch assays, and transwell chamber invasion assays, respectively. Results indicated that the positive expression rate of MTA1 protein in the medulloblastoma tissues was higher as compared with that of the adjacent normal tissues (P medulloblastoma cells, while MTA1 knockdown in medulloblastoma cells inhibited MTA1 expression. In addition, MTA1 knockdown inhibited the adhesion, migration, and invasive capabilities of medulloblastoma cells. It is possible that MTA1 can serve as a biomarker and a potential therapeutic target for medulloblastoma.

  6. Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.

    Science.gov (United States)

    Corno, Daniela; Daniela, Corno; Pala, Mauro; Cominelli, Manuela; Cipelletti, Barbara; Leto, Ketty; Croci, Laura; Barili, Valeria; Brandalise, Federico; Melzi, Raffaella; Di Gregorio, Alessandra; Sergi, Lucia Sergi; Politi, Letterio Salvatore; Piemonti, Lorenzo; Bulfone, Alessandro; Rossi, Paola; Rossi, Ferdinando; Consalez, Gian Giacomo; Poliani, Pietro Luigi; Galli, Rossella

    2012-06-01

    Medulloblastoma arises from mutations occurring in stem/progenitor cells located in restricted hindbrain territories. Here we report that the mouse postnatal ventricular zone lining the IV ventricle also harbors bona fide stem cells that, remarkably, share the same molecular profile with cerebellar white matter-derived neural stem cells (NSC). To identify novel molecular mediators involved in medulloblastomagenesis, we compared these distinct postnatal hindbrain-derived NSC populations, which are potentially tumor initiating, with murine compound Ptch/p53 mutant medulloblastoma cancer stem cells (CSC) that faithfully phenocopy the different variants of human medulloblastoma in vivo. Transcriptome analysis of both hindbrain NSCs and medulloblastoma CSCs resulted in the generation of well-defined gene signatures, each reminiscent of a specific human medulloblastoma molecular subclass. Most interestingly, medulloblastoma CSCs upregulated developmentally related genes, such as Ebfs, that were shown to be highly expressed in human medulloblastomas and play a pivotal role in experimental medullo-blastomagenesis. These data indicate that gene expression analysis of medulloblastoma CSCs holds great promise not only for understanding functional differences between distinct CSC populations but also for identifying meaningful signatures that might stratify medulloblastoma patients beyond histopathologic staging.

  7. Extraneural metastases of medulloblastoma: desmoplastic variants may have prolonged survival.

    Science.gov (United States)

    Young, Robert J; Khakoo, Yasmin; Yhu, Stephen; Wolden, Suzanne; De Braganca, Kevin C; Gilheeney, Stephen W; Dunkel, Ira J

    2015-04-01

    Extraneural metastases from CNS medulloblastoma are rare and poorly described. The purpose of this study is to describe the clinical and radiological characteristics of a large single institution series of patients with medulloblastoma who developed extraneural metastases. We retrospectively reviewed a departmental database over a 20 year period for all patients with medulloblastoma who developed extraneural metastases. Chart and imaging reviews were performed, and overall survival (OS) estimated by the Kaplan-Meier method. We found 14 patients with medulloblastoma and extraneural metastases. The median age at initial diagnosis was 16.3 years (range, 3.2-44.2), and the most common subtype was desmoplastic (n = 6, 42.9%). After initial gross total resection, most patients received radiation therapy alone (n = 10, 71.4%). Metastases to bone were most common (n = 11, 78.6%) followed by metastases to bone marrow (n = 6, 42.9%), usually to the spine. The median time from initial diagnosis to first extraneural metastasis was 1.5 years (range, 0.2-17.4), and the median OS from extraneural metastasis to death was 3.3 years (range, 0-18). The Kaplan-Meier estimate of 5 year OS from extraneural metastasis diagnosis was 40.0% (95% CI, 20.2-79.2). Extraneural metastases from medulloblastoma may rarely develop after initial diagnosis to involve bone and bone marrow. We found that desmoplastic variant extraneural tumors had longer survival than nondesmoplastic variants, suggesting that histopathological and more recent molecular subtyping have important roles in determining the prognosis of medulloblastoma patients. © 2014 Wiley Periodicals, Inc.

  8. Subdural Empyema Complicating Bacterial Meningitis: A Challenging Diagnosis in a Patient with Polysubstance Abuse

    National Research Council Canada - National Science Library

    Ramoutar, Virin Rajiv Neil; Dakkak, Melissa; Cullinane, William Russell, Jr

    2015-01-01

    Subdural empyema (SDE) and cerebrovascular accident (CVA) are uncommon life-threatening complications of bacterial meningitis, which require urgent neurosurgical intervention to prevent adverse outcomes...

  9. Ruptured Intrasellar Superior Hypophyseal Artery Aneurysm Presenting with Pure Subdural Haematoma

    Science.gov (United States)

    Hornyak, M.; Hillard, V.; Nwagwu, C.; Zablow, B. C.; Murali, R.

    2004-01-01

    Summary Subdural haemorrhage from a ruptured intracranial aneurysm is a well-known entity when associated with subarachnoid haemorrhage. However, haemorrhage confined only to the subdural space is rare because there are limited anatomical sites where extravasation can be purely subdural. We report the rare case of a patient who suffered pure subdural haematoma after the rupture of a left superior hypophyseal artery aneurysm located within the sella turcica. The patient was treated with endovascular coil embolization of the aneurysm. Angiography immediately after treatment and one month later revealed complete obliteration of the aneurysm. Six months after treatment, the patient remained symptom free. PMID:20587264

  10. PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Alok R Singh

    Full Text Available Sonic hedgehog (SHH medulloblastoma (MB subtype is driven by a proliferative CD15+ tumor propagating cell (TPC, also considered in the literature as a putative cancer stem cell (CSC. Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN and phosphoinositide 3-kinase (PI-3K play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease. Using the ND2-SmoA1 transgenic mouse model for MB, mouse genetics and patient-derived xenografts (PDXs, we demonstrate that the CD15+TPCs are 1 obligately required for SmoA1Tg-driven tumorigenicity 2 regulated by PTEN and PI-3K signaling 3 selectively sensitive to the cytotoxic effects of pan PI-3K inhibitors in vitro and in vivo but resistant to chemotherapy 4 in the SmoA1Tg mouse model are genomically similar to the SHH human MB subgroup. The results provide the first evidence that PTEN plays a role in MB TPC signaling and biology and that PI-3K inhibitors target and suppress the survival and proliferation of cells within the mouse and human CD15+ cancer stem cell compartment. In contrast, CD15+ TPCs are resistant to cisplatinum, temozolomide and the SHH inhibitor, NVP-LDE-225, agents currently used in treatment of medulloblastoma. These studies validate the therapeutic efficacy of pan PI-3K inhibitors in the treatment of CD15+ TPC dependent medulloblastoma and suggest a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease.

  11. PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma.

    Science.gov (United States)

    Singh, Alok R; Joshi, Shweta; Zulcic, Muamera; Alcaraz, Michael; Garlich, Joseph R; Morales, Guillermo A; Cho, Yoon J; Bao, Lei; Levy, Michael L; Newbury, Robert; Malicki, Denise; Messer, Karen; Crawford, John; Durden, Donald L

    2016-01-01

    Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease. Using the ND2-SmoA1 transgenic mouse model for MB, mouse genetics and patient-derived xenografts (PDXs), we demonstrate that the CD15+TPCs are 1) obligately required for SmoA1Tg-driven tumorigenicity 2) regulated by PTEN and PI-3K signaling 3) selectively sensitive to the cytotoxic effects of pan PI-3K inhibitors in vitro and in vivo but resistant to chemotherapy 4) in the SmoA1Tg mouse model are genomically similar to the SHH human MB subgroup. The results provide the first evidence that PTEN plays a role in MB TPC signaling and biology and that PI-3K inhibitors target and suppress the survival and proliferation of cells within the mouse and human CD15+ cancer stem cell compartment. In contrast, CD15+ TPCs are resistant to cisplatinum, temozolomide and the SHH inhibitor, NVP-LDE-225, agents currently used in treatment of medulloblastoma. These studies validate the therapeutic efficacy of pan PI-3K inhibitors in the treatment of CD15+ TPC dependent medulloblastoma and suggest a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease.

  12. Medulloblastoma in adulthood: prognostic factors influencing survival and recurrence.

    Science.gov (United States)

    Aragonés, M P; Magallón, R; Piqueras, C; Ley, L; Vaquero, J; Bravo, G

    1994-01-01

    Thirty adult patients presenting with medulloblastoma between 1974 and 1991 were studied and treated at Puerta de Hierro Clinic. After diagnosis, all patients were treated by surgery followed by radiotherapy and eight of them received adjuvant chemotherapy. We have studied the influence of some factors such as age, sex, location of tumour in the cerebellum, amount of surgical resection and histological variants on survival and recurrence of the disease. Only the histological type has a statistically significant influence on survival and recurrence: we have found that patients presenting classic medulloblastoma have a long survival and a long relapse-free interval.

  13. Bilateral subdural hematoma secondary to accidental dural puncture

    Directory of Open Access Journals (Sweden)

    Sofía Ramírez

    2015-08-01

    Full Text Available We report the case of a 25-year-old woman, who received epidural analgesia for labor pain and subsequently presented post-dural puncture headache. Conservative treatment was applied and epidural blood patch was performed. In the absence of clinical improvement and due to changes in the postural component of the headache, a brain imaging test was performed showing a bilateral subdural hematoma. The post-dural puncture headache is relatively common, but the lack of response to established medical treatment as well as the change in its characteristics and the presence of neurological deficit, should raise the suspicion of a subdural hematoma, which although is rare, can be lethal if not diagnosed and treated at the right time.

  14. [Staphylococcus aureus prostatic abscess and subdural empyema: a case report].

    Science.gov (United States)

    Cabrera Meirás, F; Sanchís Bonet, A; Blanco Carballo, O; Martín Parada, A; Duque Ruiz, G; Leiva Galvis, O

    2007-05-01

    To report one case of prostatic abscess and subdural empyema by Staphylococcus aureus. We describe the case of a 51 year old male patient who was diagnosed of prostatic abscess and subdural empyema by Staphilococcus aureus. We use clinical presentation and physical exploration based on rectal digital examination, as diagnostic approach method. And computerized axial tomography and transrectal ultrasonography, which allows the guided needle drainage of the abscess, as diagnostic confirmation methods. The clinical picture resolved with the transrectal ultrasonography guided needle aspiration of the abscess and conservative treatment with antibiotics and urinary diversion. Prostatic abscess is an uncommon entity nowadays. Provided the great variety of symptoms, a great degree of clinical suspicion is needed for the diagnosis, and once it is got it, immediate aggressive treatment must be initiated. Transrectal ultrasonography allows not only the diagnosis, but also the drainage of the abscess. The culture of the obtained material identifies the etiological agent and the most specific antibiotic therapy.

  15. A rare complication of spinal anesthesia: Intracranial subdural hemorrhage

    Directory of Open Access Journals (Sweden)

    Cengiz Kaplan

    2015-02-01

    Full Text Available Spinal (subarachnoid anesthesia (SA is a widely used general-purpose anesthesia. Postdural Puncture Headaches (PDPHs represent one of the principal complications of spinal anesthesia. A 21-year-old man underwent inguinal herniorrhaphy and orchiectomy using spinal anesthesia. Postoperatively, our patient started to have a headache with nausea. The patient received symptomatic therapy, but the severe headache persisted even in the supine position, with his vital signs and neurological examination being normal. Cranial MRI showed a bilateral subdural hematoma from his frontal to temporal region. A postdural puncture headache is a frequent complication after spinal anesthesia. However, serious complications, such as an intracranial subdural hemorrhage, can rarely occur. [Arch Clin Exp Surg 2015; 4(1.000: 54-56

  16. Epigenetic Silencing of DKK3 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    André Oberthuer

    2013-04-01

    Full Text Available Medulloblastoma (MB is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK 1–4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001. Since copy number aberrations targeting the DKK3 locus (11p15.3 are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA, a potent inhibitor of histone deacetylases (HDAC, was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation.

  17. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1 +/− p53 −/− mice

    National Research Council Canada - National Science Library

    Romer, Justyna T; Kimura, Hiromichi; Magdaleno, Susan; Sasai, Ken; Fuller, Christine; Baines, Helen; Connelly, Michele; Stewart, Clinton F; Gould, Stephen; Rubin, Lee L; Curran, Tom

    2004-01-01

    ... for medulloblastoma; we show that suppression of the Sonic Hedgehog pathway can be an effective treatment for this tumor. Introduction Research in molecular oncology has benefited from the advent of mouse models of human cancer (Hesselager and Holland, 2003; Van Dyke and Jacks, 2002) . Genetically engineered mouse strains have been used t...

  18. Subdural Hematoma in Grave’s Disease Induced Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2013-01-01

    Full Text Available Subdural hematoma (SDH usually occurs secondary to trauma, in bleeding disorders it may occur spontaneously. It is a rare complication of immune thrombocytopenia. Here we report a case of 45 years female presenting with presenting with complaints of headache, palpitation and menorrhagia and later diagnosed to be a case of Grave's disease with thrombocytopenia with sub dural hematoma. No such case reports are available in literature.

  19. Chronic subdural haematoma in patients with Huntington's disease.

    Science.gov (United States)

    Pechlivanis, I; Andrich, J; Scholz, M; Harders, A; Saft, C; Schmieder, K

    2006-10-01

    We studied the frequency of patients who had chronic subdural haematomas (CSDH) and Huntington's disease (HD) in a 1-year study period. In our department a total of 58 patients with CSDH were treated. Four patients (6.9% of them) had HD. Surgical evacuation of the haematoma was performed in all four cases with the use of a twist drill trepanation without a drainage system.

  20. Chronic spinal subdural hematoma; Spinales chronisches subdurales Haematom

    Energy Technology Data Exchange (ETDEWEB)

    Hagen, T.; Lensch, T. [Radiologengemeinschaft, Augsburg (Germany)

    2008-10-15

    Compared with spinal epidural hematomas, spinal subdural hematomas are rare; chronic forms are even more uncommon. These hematomas are associated not only with lumbar puncture and spinal trauma, but also with coagulopathies, vascular malformations and tumors. Compression of the spinal cord and the cauda equina means that the patients develop increasing back or radicular pain, followed by paraparesis and bladder and bowel paralysis, so that in most cases surgical decompression is carried out. On magnetic resonance imaging these hematomas present as thoracic or lumbar subdural masses, their signal intensity varying with the age of the hematoma. We report the clinical course and the findings revealed by imaging that led to the diagnosis in three cases of chronic spinal subdural hematoma. (orig.) [German] Spinale subdurale Haematome sind im Vergleich zu epiduralen Haematomen selten, chronische Verlaufsformen noch seltener. Ursaechlich sind neben Lumbalpunktionen und traumatischen Verletzungen auch Blutgerinnungsstoerungen, Gefaessmalformationen und Tumoren. Aufgrund der Kompression von Myelon und Cauda equina kommt es zu zunehmenden Ruecken- oder radikulaeren Schmerzen mit anschliessender Paraparese sowie einer Darm- und Blasenstoerung, weshalb in den meisten Faellen eine operative Entlastung durchgefuehrt wird. Magnetresonanztomographisch stellen sich die Haematome meist als thorakale bzw. lumbale subdurale Raumforderungen dar, die Signalintensitaet variiert mit dem Blutungsalter. Wir berichten ueber den klinischen Verlauf und die bildgebende Diagnostik von 3 Patienten mit spinalen chronischen subduralen Haematomen. (orig.)

  1. Dynamics of subdural hygroma following decompressive craniectomy: a comparative study.

    Science.gov (United States)

    Aarabi, Bizhan; Chesler, David; Maulucci, Christopher; Blacklock, Tiffany; Alexander, Melvin

    2009-06-01

    This retrospective comparative cohort study was aimed at discovering the risk factors associated with subdural hygroma (SDG) following decompressive craniectomy (DC) to relieve intracranial hypertension in severe head injury. Sixty-eight of 104 patients who had undergone DC during a 48-month period and survived > 30 days were eligible for this study. To assess the dynamics of subdural fluid collections, the authors compared CT scanning data from and the characteristics of 39 patients who had SDGs with the data in 29 patients who did not have hygromas. Variables significant in the appearance, evolution, and resolution of this complication were analyzed in a 36-week longitudinal study. The earliest imaging evidence of SDG was seen during the 1st week after DC. The SDG volume peaked between Weeks 3 and 4 post-DC and was gradually resolved by the 17th week. Among the mechanisms of injury, motor vehicle accidents were most often linked to the development of an SDG after DC (p SDGs were ipsilateral to the side of the craniectomy, and 3 (8%) of 39 SDGs showed evidence of internal bleeding at approximately 8 weeks postinjury. Surgical evacuation was needed in 4 patients with SDGs. High dynamic accidents and patients with diffuse injury were more prone to SDGs. Close to 8% of SDGs converted themselves into subdural hematomas at approximately 2 months postinjury. Although SDGs developed in 39 (approximately 60%) of 68 post-DC patients, surgical evacuation was needed in only 4.

  2. Involvement of Wnt signaling pathway in murine medulloblastoma induced by human neurotropic JC virus.

    Science.gov (United States)

    Gan, D D; Reiss, K; Carrill, T; Del Valle, L; Croul, S; Giordano, A; Fishman, P; Khalili, K

    2001-08-09

    By using the early genome of the human neurotropic polyomavirus, JCV, we have created transgenic animals that develop cerebellar primitive neuroectodermal tumors which model human medulloblastoma. Expression of T-antigen was found in some, but not all, tumor cells, and examination of the clonal cell lines derived from the tumor population showed enhanced tumorigenicity of cells expressing T-antigen in comparison to T-antigen negative cells. Considering the earlier notion on the potential involvement of beta-catenin with human medulloblastoma, we investigated various components of the Wnt signaling pathway including beta-catenin, its partner transcription factor, LEF-1, and their downstream target gene c-myc in these two cell populations. Immunohistochemical staining of the cells revealed enhanced nuclear appearance of beta-catenin in T-antigen positive cells. Results from Western blot showed higher levels of beta-catenin and LEF-1 in T-antigen positive cells in comparison to those in T-antigen negative cells. The enhanced level of LEF-1 expression correlated with the increase in DNA binding activity of this protein in nuclear extracts of T-antigen positive cells. Results from Northern and Western blot analyses revealed that the level of c-myc expression is augmented both at the RNA and protein levels in T-antigen positive cells. These observations corroborated results from transfection studies indicating the ability of JCV T-antigen to stimulate c-myc promoter activity. Further, co-transfection experiments revealed that the amount of c-myc and T-antigen protein in tumor cells may dictate the activity of JCV early promoter in these cells. These observations are interesting in light of recent discoveries on the association of JCV with human medulloblastoma and suggest that communication between JCV and the Wnt pathway may be an important event in the genesis of these tumors.

  3. Tratamiento médico de un hematoma subdural crónico Medical treatment of a chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Antonio Guevara Melcón

    2012-03-01

    Full Text Available Se presenta una paciente portadora de un hematoma subdural crónico postraumático, que se trató médicamente y se logró su desaparición en el curso de varios meses, sin tratamiento quirúrgico y sin signos evolutivos de empeoramiento neurológico. La furosemida fue usada como medicamento básico en su tratamiento. Se adjuntan imágenes que confirman el valor de este punto de vista terapéutico.This is the case of a patient carrier of a post-traumatic chronic subdural hematoma clinically treated achieving its disappearance over some months without surgical treatment and evolutionary signs of neurologic worsening. The furosemide was used as basic drug in its treatment. The images confirming the value of this point of therapeutical view are enclosed.

  4. Comprehensive high-resolution genomic profiling and cytogenetics of two pediatric and one adult medulloblastoma.

    Science.gov (United States)

    Holland, Heidrun; Xu, Li-Xin; Ahnert, Peter; Kirsten, Holger; Koschny, Ronald; Bauer, Manfred; Schober, Ralf; Meixensberger, Jürgen; Krupp, Wolfgang

    2013-09-01

    Medulloblastoma (WHO grade IV) is a rare, malignant, invasive, embryonal tumor which mainly occurs in children and represents less than 1% of all adult brain tumors. Systematic comprehensive genetic analyses on medulloblastomas are rare but necessary to provide more detailed information. Therefore, we performed comprehensive cytogenetic analyses (blood and tissue) of two pediatric and one adult medulloblastoma, using trypsin-Giemsa staining, spectral karyotyping (tissues only), SNP-arrays, and gene expression analyses. We confirmed frequently detected chromosomal aberrations in medulloblastoma, such as +7q, -8p/q, -9q, -11q, -12q, and +17q and identified novel genetic events. Applying SNP-array, we identified constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12 (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1-16p11.2, 18p11.32, Yq11.223-Yq11.23 (pediatric medulloblastoma), Xp22.31 (adult medulloblastoma) possibly representing inherited causal events for medulloblastoma formation. We show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3, and 17q22 not previously described for primary medulloblastoma. Gene expression analysis supported classification of the adult medulloblastoma to the WNT-subgroup and classification of pediatric medulloblastomas to group 3 tumors. Analyses of tumors and matched normal tissues (blood) with a combination of complementary techniques will help to further elucidate potentially causal genetic events for medulloblastomas. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. The whole-genome landscape of medulloblastoma subtypes

    NARCIS (Netherlands)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A.; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T. W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M. G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J. M.; Witt, Olaf; Milde, Till; von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

    2017-01-01

    Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and

  6. The whole-genome landscape of medulloblastoma subtypes

    DEFF Research Database (Denmark)

    Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana

    2017-01-01

    Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes ...

  7. Cystic Medulloblastoma in a child | Agrawal | East and Central ...

    African Journals Online (AJOL)

    East and Central African Journal of Surgery. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 14, No 1 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Cystic Medulloblastoma in a child. A Agrawal, A Agrawal, DN ...

  8. Clonal selection drives genetic divergence of metastatic medulloblastoma

    NARCIS (Netherlands)

    Wu, Xiaochong; Northcott, Paul A.; Dubuc, Adrian; Dupuy, Adam J.; Shih, David J. H.; Witt, Hendrik; Croul, Sidney; Bouffet, Eric; Fults, Daniel W.; Eberhart, Charles G.; Garzia, Livia; van Meter, Timothy; Zagzag, David; Jabado, Nada; Schwartzentruber, Jeremy; Majewski, Jacek; Scheetz, Todd E.; Pfister, Stefan M.; Korshunov, Andrey; Li, Xiao-Nan; Scherer, Stephen W.; Cho, Yoon-Jae; Akagi, Keiko; MacDonald, Tobey J.; Koster, Jan; McCabe, Martin G.; Sarver, Aaron L.; Collins, V. Peter; Weiss, William A.; Largaespada, David A.; Collier, Lara S.; Taylor, Michael D.

    2012-01-01

    Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord(1). Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis

  9. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

    Science.gov (United States)

    Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

    2016-01-01

    Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

  10. Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.

    Science.gov (United States)

    Williams, Scott E; Garcia, Idoia; Crowther, Andrew J; Li, Shiyi; Stewart, Alyssa; Liu, Hedi; Lough, Kendall J; O'Neill, Sean; Veleta, Katherine; Oyarzabal, Esteban A; Merrill, Joseph R; Shih, Yen-Yu Ian; Gershon, Timothy R

    2015-11-15

    Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma. © 2015. Published by The Company of Biologists Ltd.

  11. Time Perception in Children Treated for a Cerebellar Medulloblastoma

    Science.gov (United States)

    Droit-Volet, Sylvie; Zelanti, Pierre S.; Dellatolas, Georges; Kieffer, Virginie; El Massioui, Nicole; Brown, Bruce L.; Doyere, Valerie; Provasi, Joelle; Grill, Jacques

    2013-01-01

    The aim of the present study was to investigate temporal abilities in children treated by surgery for a malignant tumor in the cerebellum. Children with a diagnosed medulloblastoma and age-paired control children were given a temporal discrimination task (bisection task) and a temporal reproduction task with two duration ranges, one shorter than 1…

  12. Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma.

    Science.gov (United States)

    Koto, Karen S; Lescault, Pamela; Brard, Laurent; Kim, Kyukwang; Singh, Rakesh K; Bond, Jeff; Illenye, Sharon; Slavik, Marni A; Ashikaga, Takamaru; Saulnier Sholler, Giselle L

    2011-05-01

    Medulloblastoma, a neuroectodermal tumor arising in the cerebellum, is the most common brain tumor found in children. We recently showed that nifurtimox induces production of reactive oxygen species (ROS) and subsequent apoptosis in neuroblastoma cells both in vitro and in vivo. Tetrathiomolybdate (TM) has been shown to decrease cell proliferation by inhibition of superoxide dismutase-1 (SOD1). Since both nifurtimox and TM increase ROS levels in cells, we investigated whether the combination of nifurtimox and TM would act synergistically in medulloblastoma cell lines (D283, DAOY). Genome-wide transcriptional analysis, by hybridizing RNA isolated from nifurtimox and TM alone or in combination treated and control cells (D283) on Affymetrix exon array gene chips was carried out to further confirm synergy. We show that nifurtimox and TM alone and in combination decreased cell viability and increased ROS levels synergistically. Examination of cell morphology following drug treatment (nifurtimox + TM) and detection of caspase-3 activation via Western blotting indicated that cell death was primarily due to apoptosis. Microarray data from cells treated with nifurtimox and TM validated the induction of oxidative stress, as many Nrf2 target genes (HMOX1, GCLM, SLC7A11 and SRXN1) (pnifurtimox + TM. Taken together, our results suggest nifurtimox and TM act synergistically in medulloblastoma cells in vitro, and that this combination warrants further studies as a new treatment for medulloblastoma.

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

    Science.gov (United States)

    Thompson, Eric M; Hielscher, Thomas; Bouffet, Eric; Remke, Marc; Luu, Betty; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Lipp, Eric S; Perreault, Sebastien; Cho, Yoon-Jae; Grant, Gerald; Kim, Seung-Ki; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Li, Kay Ka Wai; Ng, Ho-Keung; Yao, Yu; Kumabe, Toshihiro; Tominaga, Teiji; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Low, David C Y; Seow, Wan Tew; Chang, Kenneth T E; Mora, Jaume; Pollack, Ian F; Hamilton, Ronald L; Leary, Sarah; Moore, Andrew S; Ingram, Wendy J; Hallahan, Andrew R; Jouvet, Anne; Fèvre-Montange, Michelle; Vasiljevic, Alexandre; Faure-Conter, Cecile; Shofuda, Tomoko; Kagawa, Naoki; Hashimoto, Naoya; Jabado, Nada; Weil, Alexander G; Gayden, Tenzin; Wataya, Takafumi; Shalaby, Tarek; Grotzer, Michael; Zitterbart, Karel; Sterba, Jaroslav; Kren, Leos; Hortobágyi, Tibor; Klekner, Almos; László, Bognár; Pócza, Tímea; Hauser, Peter; Schüller, Ulrich; Jung, Shin; Jang, Woo-Youl; French, Pim J; Kros, Johan M; van Veelen, Marie-Lise C; Massimi, Luca; Leonard, Jeffrey R; Rubin, Joshua B; Vibhakar, Rajeev; Chambless, Lola B; Cooper, Michael K; Thompson, Reid C; Faria, Claudia C; Carvalho, Alice; Nunes, Sofia; Pimentel, José; Fan, Xing; Muraszko, Karin M; López-Aguilar, Enrique; Lyden, David; Garzia, Livia; Shih, David J H; Kijima, Noriyuki; Schneider, Christian; Adamski, Jennifer; Northcott, Paul A; Kool, Marcel; Jones, David T W; Chan, Jennifer A; Nikolic, Ana; Garre, Maria Luisa; Van Meir, Erwin G; Osuka, Satoru; Olson, Jeffrey J; Jahangiri, Arman; Castro, Brandyn A; Gupta, Nalin; Weiss, William A; Moxon-Emre, Iska; Mabbott, Donald J; Lassaletta, Alvaro; Hawkins, Cynthia E; Tabori, Uri; Drake, James; Kulkarni, Abhaya; Dirks, Peter; Rutka, James T; Korshunov, Andrey; Pfister, Stefan M; Packer, Roger J; Ramaswamy, Vijay; Taylor, Michael D

    2016-04-01

    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. We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival

  14. Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors.

    Science.gov (United States)

    Whitby, E H; Griffiths, P D; Rutter, S; Smith, M F; Sprigg, A; Ohadike, P; Davies, N P; Rigby, A S; Paley, M N

    2004-03-13

    Subdural haematomas are thought to be uncommon in babies born at term. This view is mainly based on findings in symptomatic neonates and babies in whom subdural haemorrhages are detected fortuitously. We aimed to establish the frequency of subdural haemorrhages in asymptomatic term neonates; to study the natural history of such subdural haematomas; and to ascertain which obstetric factors, if any, are associated with presence of subdural haematoma. We did a prospective study in babies who were born in the Jessop wing of the Central Sheffield University Hospitals between March, 2001, and November, 2002. We scanned neonates with a 0.2 T magnetic resonance machine. 111 babies underwent MRI in this study. 49 were born by normal vertex delivery without instrumentation, 25 by caesarean section, four with forceps, 13 ventouse, 18 failed ventouse leading to forceps, one failed ventouse leading to caesarean section, and one failed forceps leading to caesarean section. Nine babies had subdural haemorrhages: three were normal vaginal deliveries (risk 6.1%), five were delivered by forceps after an attempted ventouse delivery (27.8%), and one had a traumatic ventouse delivery (7.7%). All babies with subdural haemorrhage were assessed clinically but no intervention was needed. All were rescanned at 4 weeks and haematomas had completely resolved. Presence of unilateral and bilateral subdural haemorrhage is not necessarily indicative of excessive birth trauma.

  15. Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations.

    Science.gov (United States)

    Zuzak, T J; Rist, L; Eggenschwiler, J; Grotzer, M A; Viviani, A

    2006-01-01

    Medulloblastoma constitute more than 20% of all paediatric brain tumours and are the most common malignant brain tumours in children. Adjuvant chemotherapy has seen a strong increase in the use of complementary medicine for cancer treatment. Evidence for cytotoxic and apoptotic effects of Viscum album (Mistletoe) in vitro is available, however, no data concerning paediatric tumours, especially paediatric brain tumours, has been provided so far. In order to compare the receptiveness of medulloblastoma cells to different Viscum album preparations, in vitro cytotoxic effects of eight Viscum album extracts on four different paediatric medulloblastoma cell lines were analysed by MTT-Tests. Lectin contents of the extracts were determined to correlate them with the mitochondrial activity of mistletoe-treated cells. Flowcytometric analyses with Annexin V-FITC staining were carried out to quantify the amount of apoptotic cells compared to necrotic and viable cells. Data obtained with the medulloblastoma cell lines, Daoy, D342, D425 and UW-288-2, treated with Viscum album preparations from eight dissimilar host trees (Iscucin Abietis, Pini, Populi, Mali, Salicis, Crataegi, Quercus and Tiliae), indicated a significant growth-inhibition of all cell lines, yet the cell susceptibility was dissimilar against the different extracts. The decrease in mitochondrial activity and increase in apoptosis correlated with the lectin content of the used preparation in a dose-dependent manner. These in vitro results show that paediatric medulloblastoma cells respond to Viscum album preparations, by undergoing cell death through apoptosis and that this growth-inhibition correlates with the lectin content of the used preparation.

  16. Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours

    NARCIS (Netherlands)

    von Bueren, A. O.; Bacolod, M. D.; Hagel, C.; Heinimann, K.; Fedier, A.; Kordes, U.; Pietsch, T.; Koster, J.; Grotzer, M. A.; Friedman, H. S.; Marra, G.; Kool, M.; Rutkowski, S.

    2012-01-01

    BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in O-6-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA

  17. Oncolytic Herpes Virus rRp450 Shows Efficacy in Orthotopic Xenograft Group 3/4 Medulloblastomas and Atypical Teratoid/Rhabdoid Tumors

    Directory of Open Access Journals (Sweden)

    Adam W. Studebaker

    2017-09-01

    Full Text Available Pediatric brain tumors including medulloblastoma and atypical teratoid/rhabdoid tumor are associated with significant mortality and treatment-associated morbidity. While medulloblastoma tumors within molecular subgroups 3 and 4 have a propensity to metastasize, atypical teratoid/rhabdoid tumors frequently afflict a very young patient population. Adjuvant treatment options for children suffering with these tumors are not only sub-optimal but also associated with many neurocognitive obstacles. A potentially novel treatment approach is oncolytic virotherapy, a developing therapeutic platform currently in early-phase clinical trials for pediatric brain tumors and recently US Food and Drug Administration (FDA-approved to treat melanoma in adults. We evaluated the therapeutic potential of the clinically available oncolytic herpes simplex vector rRp450 in cell lines derived from medulloblastoma and atypical teratoid/rhabdoid tumor. Cells of both tumor types were supportive of virus replication and virus-mediated cytotoxicity. Orthotopic xenograft models of medulloblastoma and atypical teratoid/rhabdoid tumors displayed significantly prolonged survival following a single, stereotactic intratumoral injection of rRp450. Furthermore, addition of the chemotherapeutic prodrug cyclophosphamide (CPA enhanced rRp450’s in vivo efficacy. In conclusion, oncolytic herpes viruses with the ability to bioactivate the prodrug CPA within the tumor microenvironment warrant further investigation as a potential therapy for pediatric brain tumors.

  18. Spontaneous acute subdural hematoma as the initial manifestation of chronic myeloid leukemia.

    Science.gov (United States)

    Abdulhamid, Mohamed M; Li, Yan Michael; Hall, Walter A

    2011-02-01

    Spontaneous acute subdural hematoma is rare and limited to sporadic case reports, associated with neoplasm, aneurysm, arteriovenous malformation and cocaine use. Subdural hematoma has also been reported in association with leukemic malignancies, either during therapy or after diagnosis. However, there are no reports of spontaneous acute subdural hematoma as the primary initial presenting manifestation of a chronic myeloid leukemia. Here we describe one case of a 53-year-old male that presented with severe right-sided headache and intermittent left-sided paresthesias. CT scan showed non-traumatic right-sided acute subdural hematoma. Further evaluation revealed that the patient had chronic myeloid leukemia. His peripheral white blood count normalized after Gleevec and hydroxyurea chemotherapy. Furthermore, he had no neurological deficits after his subdural collection was adequately evacuated.

  19. Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans

    OpenAIRE

    Pöschl, J; Lorenz, A; Hartmann, W.; Von Bueren, AO; Kool, M; S. Li; Peraud, A.; Tonn, J-C; Herms, J; Xiang, M.; Rutkowski, S; Kretzschmar, HA; Schüller, U.

    2011-01-01

    Medulloblastoma is the most common malignant brain tumor in childhood, and development of targeted therapies is highly desired. Although the molecular mechanisms of malignant transformation are not fully understood, it is known that medulloblastomas may arise from cerebellar granule neuron precursors. The homeodomain transcription factor Barhl1 is known to regulate migration and survival of granule cell precursors, but its functional role in medulloblastoma is unknown. We show here that the e...

  20. Adjuvant chemotherapy and overall survival in adult medulloblastoma.

    Science.gov (United States)

    Kann, Benjamin H; Lester-Coll, Nataniel H; Park, Henry S; Yeboa, Debra N; Kelly, Jacqueline R; Baehring, Joachim M; Becker, Kevin P; Yu, James B; Bindra, Ranjit S; Roberts, Kenneth B

    2017-02-01

    Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

  1. High expression of BAG3 predicts a poor prognosis in human medulloblastoma.

    Science.gov (United States)

    Yang, Dong; Zhou, Ji; Wang, Hao; Wang, Yutao; Yang, Ge; Zhang, Yundong

    2016-10-01

    Bcl2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock protein (Hsp) 70, regulates various physiological and pathological processes. However, its role in human medulloblastoma has not been clarified. First of all, the expression of BAG3 was examined in formalin-fixed, paraffin-embedded specimens by immunohistochemical staining. And then, the prognostic role of BAG3 was analyzed in 51 medulloblastoma samples. Finally, the roles of BAG3 in the proliferation, migration, and invasion of Daoy medulloblastoma cell were investigated using a specific short hairpin RNA (shRNA). The expression of BAG3 in medulloblastoma tissues was higher than nontumorous samples. Furthermore, BAG3 overexpression significantly correlated with poor prognosis of patients with medulloblastoma. The overall survival and tumor-free survival in patients with BAG3 low expression were higher than high expression. Univariate and multivariate analysis showed that BAG3 overexpression was an independent prognostic marker for medulloblastoma. After the BAG3 knockdown, the Daoy cells exhibited decreased the ability to proliferate and form neurosphere. The preliminary mechanism study showed that overexpression of BAG3 might facilitate the cell cycle transition from G1 to S phase by modulating the cyclin-dependent kinase 2 (CDK2) and cyclin E expression. Additionally, we found that BAG3 might enhance the medulloblastoma cell migratory and invasive ability. In summary, BAG3 overexpression may regulate the survival and invasive properties of medulloblastoma and may serve as a potential therapy target for medulloblastoma.

  2. Coleção subdural na criança: fisiopatologia e tratamento Subdural effusions in children: pathophysiology and treatment

    Directory of Open Access Journals (Sweden)

    Sebastião Gusmão

    1997-06-01

    Full Text Available Nove crianças portadoras de coleção subdural (CSD foram tratadas por meio de derivação subduro-peritoneal. Todas foram submetidas a controle com tomografia computadorizada do encéfalo. O tamanho da coleção subdural foi avaliado por medida de sua área no corte tomográfico por meio de morfologia quantitativa com planímetro. Ocorreu regressão completa ou quase completa da CSD em oito pacientes. Os resultados funcionais foram excelentes em quatro pacientes, bons em três e maus em dois. Foi feita uma revisão da fisiopatologia e do tratamento da CSD na criança.Nine children harboring subdural effusions were treated by subduro peritoneal shunt. These patients were followed-up by CT scans. The area of the subdural effusions was measured by quantitative morphology with a planimeter. With the surgical treatment, the subdural effusion disappeared completely or near completely in 8 patients. The patient's functional state were excellent in 4, good in 3 and bad in 2 in the postoperative follow-up. We aldo reviewed the literature as far as the pathophysiology and the treatment of the subdural effusions are concerned.

  3. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

    Science.gov (United States)

    Schwalbe, Edward C; Lindsey, Janet C; Nakjang, Sirintra; Crosier, Stephen; Smith, Amanda J; Hicks, Debbie; Rafiee, Gholamreza; Hill, Rebecca M; Iliasova, Alice; Stone, Thomas; Pizer, Barry; Michalski, Antony; Joshi, Abhijit; Wharton, Stephen B; Jacques, Thomas S; Bailey, Simon; Williamson, Daniel; Clifford, Steven C

    2017-07-01

    International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MBWNT remained unchanged and each remaining consensus subgroup was split in two. MBSHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MBSHH-Infant; n=65) and

  4. EZH2-Regulated DAB2IP Is a Medulloblastoma Tumor Suppressor and a Positive Marker for Survival

    NARCIS (Netherlands)

    Smits, Michiel; van Rijn, Sjoerd; Hulleman, Esther; Biesmans, Dennis; van Vuurden, Dannis G.; Kool, Marcel; Haberler, Christine; Aronica, Eleonora; Vandertop, W. Peter; Noske, David P.; Würdinger, Thomas

    2012-01-01

    Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches. Experimental

  5. Empiema espinhal subdural relato de um caso: case report

    OpenAIRE

    Magalhães,Gerson Canedo de; Rocha,José Roberto Coelho da; Souza,Luís Alberto M.; Salomão,José Francisco; Jevoux,Carla; Carneiro,Welmer

    1995-01-01

    A raridade do empiema subdural pode ser verflcada pela escassez de casos descritos na literatura. Os autores apresentam mais um caso, mostrando as dificuldades diagnosticas principalmente quando não há aparente porta de entrada. Enfatizam, nestas circunstâncias, a importância de certos sinais clínicos, o valor da punção lombar e da imagem por ressonância nuclear magnética na elucidação diagnóstica. Este último exame não foi mencionado anteriormente na literatura consultada sobre o assunto. O ...

  6. Fertility in male medulloblastoma survivors: closing the gaps in counseling

    Directory of Open Access Journals (Sweden)

    Nahata L

    2013-12-01

    Full Text Available Leena Nahata,1 Richard N Yu,2 Ian P Dumont,3,4 Peter E Manley,3,4 Laurie E Cohen1,3,4 1Division of Endocrinology, 2Department of Urology, Department of Medicine, Boston Children's Hospital, 3Division of Hematology/Oncology, Department of Medicine, Boston Children's Hospital, 4Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Background: Pediatric medulloblastoma patients have high survival rates and are at risk for treatment-related sequelae, including infertility, emphasizing the need for fertility counseling. This cohort is less likely to pursue higher education, marry, and live independently, which may impact fertility counseling. Our goal was to explore fertility-related concerns in medulloblastoma survivors and counseling practices among providers. Methods: This study was performed at the Dana-Farber/Children's Hospital Cancer Center in Boston, Massachusetts. Surveys were administered to male pediatric medulloblastoma survivors aged 18 years and older and pediatric neuro-oncology practitioners. Medical records were reviewed to determine treatment protocols and documentation of fertility counseling. Data analysis was descriptive. Results: Fourteen male medulloblastoma survivors and six neuro-oncology practitioners completed the study. All patients had received central nervous system irradiation and adjuvant chemotherapy with at least one alkylating agent. Five (83% practitioners stated that they discussed fertility with all survivors at most visits. Eight (57% medulloblastoma survivors stated that they had received fertility counseling at initial diagnosis. Six (43% stated that fertility had been discussed since treatment had ended. The majority (>70% of survivors reported a desire to have children and were open to learning more about their fertility status. Fertility counseling was documented in survivorship visits in only 46% of subjects. Conclusion: Most of our subjects had no documented fertility

  7. Bilateral chronic subdural hematoma: unilateral or bilateral drainage?

    Science.gov (United States)

    Andersen-Ranberg, Nina Christine; Poulsen, Frantz Rom; Bergholt, Bo; Hundsholt, Torben; Fugleholm, Kåre

    2017-06-01

    OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors are associated with the retreatment of bCSDH with a focus on surgical laterality. METHODS In a national database of CSDHs (Danish Chronic Subdural Hematoma Study) the authors retrospectively identified all bCSDHs treated in the 4 Danish neurosurgical departments over the 3-year period from 2010 to 2012. Univariate and multivariate analyses were performed to determine the relationship between retreatment of bCSDH and clinical, radiological, and surgical variables. RESULTS Two hundred ninety-one patients with bCSDH were identified, and 264 of them underwent unilateral (136 patients) or bilateral (128 patients) surgery. The overall retreatment rate was 21.6% (57 of 264 patients). Cases treated with unilateral surgery had twice the risk of retreatment compared with cases undergoing bilateral surgery (28.7% vs 14.1%, respectively, p = 0.002). In accordance with previous studies, the data also showed that a separated hematoma density and the absence of postoperative drainage were independent predictors of retreatment. CONCLUSIONS In bCSDHs bilateral surgical intervention significantly lowers the risk of retreatment compared with unilateral intervention and should be considered when choosing a surgical procedure.

  8. [Evolution of the management of pediatric and adult medulloblastoma].

    Science.gov (United States)

    Vigneron, C; Entz-Werlé, N; Lutz, P; Spiegel, A; Jannier, S; Helfre, S; Alapetite, C; Coca, A; Kehrli, P; Noël, G

    2015-08-01

    Medulloblastoma are cerebellar tumours belonging to the group of primitive neuroectodermal tumours (PNET) and are the most common malignant brain tumours of childhood. These tumours are rare and heterogeneous, requiring some multicentric prospective studies and multidisciplinary care. The classical therapeutic approaches are based on clinical, radiological and surgical data. They involve surgery, radiation therapy and chemotherapy. Some histological features were added to characterize risk. More recently, molecular knowledge has allowed to devise risk-adapted strategies and helped to define groups with good outcome and reduce long-term sequelae, improve the prognostic of high-risk medulloblastoma and develop new therapeutic tools. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  9. Spinal metastasis of medulloblastoma in adults: A case report

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2014-01-01

    Full Text Available Introduction. Medulloblastoma is a primitive neuro-ectodermal malignant tumor most commonly seen in childhood and rarely and uncommonly in adult age. Treatment consists of surgery followed by radiotherapy. In the case of a relapse there is no overall accepted treatment. Tumor metastasis can be seen along the neural axis, lymph nodes, soft tissues, bones and distant organs. Case Outline. In this paper we present a 45-year-old female patient with a thoraco-spinal extramedullary metastatic medulloblastoma and progressive neurological deterioration seen 11 months after the first operation and description of magnetic resonance and intraoperative finding. Conclusion. Although rare, the presence of metastasis is a poor prognostic factor. The treatment options for patients with metastases are limited and their prognosis continues to remain poor.

  10. MEDULLOBLASTOMA IN A GRIZZLY BEAR (URSUS ARCTOS HORRIBLIS).

    Science.gov (United States)

    Mitchell, Jeffrey W; Thomovsky, Stephanie A; Chen, Annie V; Layton, Arthur W; Haldorson, Gary; Tucker, Russell L; Roberts, Gregory

    2015-09-01

    A 3-yr-old female spayed grizzly bear (Ursus arctos horribilis) was evaluated for seizure activity along with lethargy, inappetence, dull mentation, and aggressive behavior. Magnetic resonance (MR) examination of the brain revealed a contrast-enhanced right cerebellar mass with multifocal smaller nodules located in the left cerebellum, thalamus, hippocampus, and cerebrum with resultant obstructive hydrocephalus. Cerebrospinal fluid analysis revealed mild mononuclear pleocytosis, with differentials including inflammatory versus neoplastic processes. Blood and cerebrospinal fluid were also submitted for polymerase chain reaction and agar gel immunodiffusion to rule out infectious causes of meningitis/encephalitis. While awaiting these results, the bear was placed on steroid and antibiotic therapy. Over the next week, the bear deteriorated; she died 1 wk after MR. A complete postmortem examination, including immunohistochemisty, revealed the cerebellar mass to be a medulloblastoma. This is the only case report, to the authors' knowledge, describing a medulloblastoma in a grizzly bear.

  11. Clinical audit effectively bridges the evidence-practice gap in chronic subdural haematoma management.

    Science.gov (United States)

    Tailor, Jignesh; Fernando, D; Sidhu, Z; Foley, R; Abeysinghe, K D; Walsh, D C

    2017-04-01

    Placement of a subdural drain after drainage of chronic subdural haematoma (CSDH) has been shown to reduce the rate of recurrence in several randomised controlled trials (RCT). The most recently published RCT was from Cambridge, UK, in 2009. Despite class I evidence for the use of subdural drains, it is unclear whether these results have been translated into clinical practice. In this clinical audit we review the use of subdural drains in our institution before and after the publication of the 2009 RCT results. A longitudinal retrospective study was performed on all adults having burr holes for CSDH between January 2009 and January 2014. Case notes were analysed to determine subdural drain use, re-operation for CSDH recurrence and post-operative complications. The audit loop was closed with data collected from August 2015 to January 2016. Thirty-one per cent of patients had subdural drains placed at operation. Drain placement was associated with lower reoperation rates (8% vs. 17%, p = 0.021) without increasing complication rates. Drain usage doubled after publication of the Santarius et al. (2009) trial but we observed persisting and significant variability in drain utilisation by supervising consultants. The use of drains in the department increased from 35% to 75% of all cases after presentation of these results. The use of subdural drains in our unit reduced recurrence rates following drainage of CSDH and reproduced the results of a 2009 clinical trial. Although the use of subdural drains doubled in the post-trial epoch, significant variability remains in practice. Clinical audit provided an effective tool necessary to drive the implementation of subdural drain placement in our unit.

  12. Intracerebellar haematoma simulating congenital medulloblastoma during neonatal period.

    Science.gov (United States)

    Babakhouya, Abdeladim; Abourazzak, Sana; Aggouri, Mohamed; Chakour, Khalid; Chaoui, Faiz Mohamed; Hida, Moustapha; Bouharrou, Abdelhak

    2011-04-09

    The authors report a case of intracerebellar haematoma occurring during the neonatal period. A 5-day-old baby girl was admitted because of poor feeding and the anterior fontanelle was tense. CT scan of the brain revealed a round mass at the cerebellar vermis; the lesion simulated a cerebellar tumour such as a medulloblastoma. The mass was surgically removed and found to be an intracerebellar haematoma. The clinical and radiologic characteristics are discussed.

  13. Aberrant signaling pathways in medulloblastomas: a stem cell connection

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    Carolina Oliveira Rodini

    2010-12-01

    Full Text Available Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio- and chemo-resistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFβ, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers.

  14. Genetic and Epigenetic Inactivation of Kruppel-like Factor 4 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yukiko Nakahara

    2010-01-01

    Full Text Available Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4 in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR. Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.

  15. Medulloblastomas of the Cerebellum in Children: Clinicopathologic Comparison

    Directory of Open Access Journals (Sweden)

    V. V. Morgun

    2017-04-01

    Full Text Available Embryonal neuroepithelial tumours of the brain, grade IV are mainly observed in children and are characterized by rapid metastatic spread and frequent recurrence. The aim of the work is to compare structural features of medulloblastomas of the cerebellum in children of different age groups taking into account localization, metastatic spread and treatment outcomes. Materials and methods. The results of complete examination and surgical treatment of 289 children with medulloblastoma of the cerebellum at the Department of Pediatric Neurosurgery of Institute of neurosurgery named after A.P. Romodanov over the period of 1993–2013 were analysed. The children’s age ranged from 1 month to 17 years: peak of medulloblastoma detection was registered at the age of 4–7. Results. As part of the study all the patients were divided into four age groups. Younger children rarely had brainstem lesion. In children of older age brainstem lesion, invasion into cerebral aqueduct with the development of noncommunicating hydrocephalus were registered. Total resection of medulloblastoma in younger children was performed in 40 % of cases, subtotal – in 42 %, partial – in 18 %. In children of older age total resection of medulloblastoma was carried out in 36%, subtotal – in 52 %, partial – in 12 % of cases. Histological analysis of tumours involved morphological characteristics of general histoarchitecture, correlation between parenchymal and stromal component, presence of Homer Wright pseudorosettes, collonar structures, pale insulas, true ependymal rosettes, formation of braided collonar structures, prevalence of small low-differentiated structures, number of mitoses, neoangiogenesis and angioproliferation, presence of colliquative and coagulation necroses, evidence and type of invasion, lymphocytic infiltration of tumour tissue. The following variations were defined histologically: classical – 9470/3 in 34 cases (17.9 %, desmoplastic/nodular – 9471

  16. Computational Study of Subdural Cortical Stimulation: Effects of Simulating Anisotropic Conductivity on Activation of Cortical Neurons.

    Directory of Open Access Journals (Sweden)

    Hyeon Seo

    Full Text Available Subdural cortical stimulation (SuCS is an appealing method in the treatment of neurological disorders, and computational modeling studies of SuCS have been applied to determine the optimal design for electrotherapy. To achieve a better understanding of computational modeling on the stimulation effects of SuCS, the influence of anisotropic white matter conductivity on the activation of cortical neurons was investigated in a realistic head model. In this paper, we constructed pyramidal neuronal models (layers 3 and 5 that showed primary excitation of the corticospinal tract, and an anatomically realistic head model reflecting complex brain geometry. The anisotropic information was acquired from diffusion tensor magnetic resonance imaging (DT-MRI and then applied to the white matter at various ratios of anisotropic conductivity. First, we compared the isotropic and anisotropic models; compared to the isotropic model, the anisotropic model showed that neurons were activated in the deeper bank during cathodal stimulation and in the wider crown during anodal stimulation. Second, several popular anisotropic principles were adapted to investigate the effects of variations in anisotropic information. We observed that excitation thresholds varied with anisotropic principles, especially with anodal stimulation. Overall, incorporating anisotropic conductivity into the anatomically realistic head model is critical for accurate estimation of neuronal responses; however, caution should be used in the selection of anisotropic information.

  17. A compartmentalized phosphoinositide signaling axis at cilia is regulated by INPP5E to maintain cilia and promote Sonic Hedgehog medulloblastoma.

    Science.gov (United States)

    Conduit, S E; Ramaswamy, V; Remke, M; Watkins, D N; Wainwright, B J; Taylor, M D; Mitchell, C A; Dyson, J M

    2017-10-26

    Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3. INPP5E promotes SHH signaling during embryonic development via PtdIns(4,5)P2 hydrolysis at cilia, that in turn regulates the cilia recruitment of the SHH suppressor GPR161. However, the role INPP5E plays in cancer is unknown and the contribution of PI3-kinase signaling to cilia function is little characterized. Here, we reveal INPP5E promotes SHH signaling in SHH medulloblastoma by negatively regulating a cilia-compartmentalized PI3-kinase signaling axis that maintains primary cilia on tumor cells. Conditional deletion of Inpp5e in a murine model of constitutively active Smoothened-driven medulloblastoma slowed tumor progression, suppressed cell proliferation, reduced SHH signaling and promoted tumor cell cilia loss. PtdIns(3,4,5)P3, its effector pAKT and the target pGSK3β, which when non-phosphorylated promotes cilia assembly/stability, localized to tumor cell cilia. The number of PtdIns(3,4,5)P3/pAKT/pGSK3β-positive cilia was increased in cultured Inpp5e-null tumor cells relative to controls. PI3-kinase inhibition or expression of wild-type, but not catalytically inactive HA-INPP5E partially rescued cilia loss in Inpp5e-null tumor cells in vitro. INPP5E mRNA and copy number were reduced in human SHH medulloblastoma compared to other molecular subtypes and consistent with the murine model, reduced INPP5E was associated with improved overall survival

  18. Empiema espinhal subdural relato de um caso: case report

    Directory of Open Access Journals (Sweden)

    Gerson Canedo de Magalhães

    1995-03-01

    Full Text Available A raridade do empiema subdural pode ser verflcada pela escassez de casos descritos na literatura. Os autores apresentam mais um caso, mostrando as dificuldades diagnosticas principalmente quando não há aparente porta de entrada. Enfatizam, nestas circunstâncias, a importância de certos sinais clínicos, o valor da punção lombar e da imagem por ressonância nuclear magnética na elucidação diagnóstica. Este último exame não foi mencionado anteriormente na literatura consultada sobre o assunto. O tratamento cirúrgico, associado à antibioticoterapia, mostrou- se bastante eficaz, principalmente se realizado precocemente.

  19. Subdural abscess associated with halo-pin traction.

    Science.gov (United States)

    Garfin, S R; Botte, M J; Triggs, K J; Nickel, V L

    1988-10-01

    Osteomyelitis and intracranial abscess are among the most serious complications that have been reported in association with the use of the halo device. The cases of five patients who had formation of an intracranial abscess related to the use of a halo cervical immobilizer are described. All of the infections resolved after drainage of the abscess, débridement, and parenteral administration of antibiotics. Meticulous care of the pin sites is essential to avoid this serious complication. Additionally, since all of the infections were associated with prolonged halo-skeletal traction, this technique should be used with caution and with an awareness of the possible increased risks of pin-site infection and of formation of a subdural abscess.

  20. Subdural hematoma cases identified through a Danish patient register

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Halle, Bo; Pottegård, Anton

    2016-01-01

    PURPOSE: This study aimed to assess the usefulness of Danish patient registers for epidemiological studies of subdural hematoma (SDH) and to describe clinical characteristics of validated cases. METHODS: Using a patient register covering a geographically defined area in Denmark, we retrieved...... hospital contacts recorded under SDH International Classification of Diseases version 10 codes S065 and I620 in 2000-2012. Neurosurgeons reviewed medical records of all potential cases. Based on brain scan results, verified cases were classified by SDH type (chronic SDH (cSDH) or acute SDH (aSDH)). Thirty......-day mortality and preadmission antithrombotic drug use were established through linkage to population-based registers. We calculated the positive predictive value of the SDH code and compared mortality and preadmission antithrombotic drug use of cSDH with those of aSDH (age-adjusted and sex-adjusted odds ratio...

  1. Anticoagulation therapy a risk factor for the development of chronic subdural hematoma

    DEFF Research Database (Denmark)

    Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.

    2013-01-01

    Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....

  2. Kernohan-Woltman notch phenomenon and intention tremors in case of chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Sasikala P.

    2014-03-01

    Full Text Available Movement disorders are atypical and rare presentation of chronic subdural hematomas. We report a case of 60 year man who presented with intention tremors and altered sensorium. The patient had Kernohan-Woltman notch phenomenon on clinical examination. CT scan brain showed a large left fronto-temporo-parietal chronic subdural hematoma with significant mass effect and midline shift. His symptoms relieved completely after surgical evacuation of the hematoma.

  3. Spontaneous bilateral subdural haematomas in the posterior cranial fossa revealed by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Pollo, C.; Porchet, F. [Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne (Switzerland); Meuli, R. [Department of Radiology, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne (Switzerland)

    2003-08-01

    A 52-year-old woman treated for acute myeloproliferative disease developed progressive stupor. CT showed obstructive hydrocephalus resulting from unexplained mass effect on the fourth ventricle. MRI revealed bilateral extra-axial collections in the posterior cranial fossa, giving high signal on T1- and T2-weighted images, suggesting subacute subdural haematomas. Subdural haematomas can be suspected on CT when there is unexplained mass effect. MRI may be essential to confirm the diagnosis and plan appropriate treatment. (orig.)

  4. Osmotic diuresis paradoxically worsens brain shift after subdural grid placement.

    Science.gov (United States)

    Etame, Arnold B; Fox, W Christopher; Sagher, Oren

    2011-03-01

    The purpose of this study was to assess for peri-operative factors associated with brain shift following craniotomy for subdural grid electrode placement. A retrospective analysis of cases operated at a single institution was undertaken, examining 63 consecutive patients undergoing craniotomy for subdural grid placement for seizure monitoring between 2001 and 2007. Peri-operative records were reviewed in order to assess for intraoperative employment of osmotic duiresis. Postoperative MRI scans were analyzed for shift of the midline and brain displacement. One patient was excluded due to gross hemispheric atrophy confounding the midline, and four patients were excluded due to lack of available imaging. Hence 58 patients were radiographically reviewed. The employment of osmotic diuresis during grid placement appeared to be the most significant peri-operative factor influencing brain shift. Osmotic diuresis was administered in only 14 patients. Midline shift of the third ventricle was greater in the osmotic diuresis group (2.3 ± 0.3 mm vs. 1.5 ± 0.2 mm, p = 0.037). Moreover, the volume of shifted brain was significantly higher in the osmotic diuresis group (7.9 ± 0.5 cm(3) vs. 4.7 ± 0.5 cm(3), p = 0.003). There was no significant difference in the rates of neurological complications between patients who received osmotic diuresis and those who did not. Employment of osmotic diuresis during grid placement appears to be associated with a paradoxical increase in the volume of shifted brain. This may be due to a combination of the resultant "sagging" of the brain and the pressure exerted by the grid, suggesting that osmotic diuresis might not improve mass effect as intended when employed within this context.

  5. Risk-based optimization of photon and proton radiotherapy for pediatric medulloblastoma

    DEFF Research Database (Denmark)

    Brodin, Nils Patrik

    this results in irradiating a large volume of healthy tissue in these young patients. The general aim of this thesis is reducing the risk of late treatment toxicity through risk-based advanced radiotherapy optimization. We specifically investigated the use of radiobiological models to estimate late......Medulloblastoma (MB) is one of the most common brain tumors in children and most patients will survive their disease if treated with surgery, radio- and chemotherapy. This has resulted in a growing number of MB survivors who are at risk of developing severe late complications related...... to the aggressive anti-cancer therapy. Some of the most important late complications for these patients include secondary malignancies, cardiac events and neurocognitive decline. Much of the late complication risk can be attributed the craniospinal irradiation which is part of standard management, since...

  6. Epidural Hematoma Complication after Rapid Chronic Subdural Hematoma Evacuation: A Case Report

    Science.gov (United States)

    Akpinar, Aykut; Ucler, Necati; Erdogan, Uzay; Yucetas, Cem Seyho

    2015-01-01

    Patient: Male, 41 Final Diagnosis: Healty Symptoms: Headache Medication: — Clinical Procedure: Chronic subdural hematoma Specialty: Neurosurgery Objective: Diagnostic/therapeutic accidents Background: Chronic subdural hematoma generally occurs in the elderly. After chronic subdural hematoma evacuation surgery, the development of epidural hematoma is a very rare entity. Case Report: We report the case of a 41-year-old man with an epidural hematoma complication after chronic subdural hematoma evacuation. Under general anesthesia, the patient underwent a large craniotomy with closed system drainage performed to treat the chronic subdural hematoma. After chronic subdural hematoma evacuation, there was epidural leakage on the following day. Conclusions: Although trauma is the most common risk factor in young CSDH patients, some other predisposing factors may exist. Intracranial hypotension can cause EDH. Craniotomy and drainage surgery can usually resolve the problem. Because of rapid dynamic intracranial changes, epidural leakages can occur. A large craniotomy flap and silicone drainage in the operation area are key safety points for neurosurgeons and hydration is essential. PMID:26147957

  7. Inhibition of GPR137 suppresses proliferation of medulloblastoma cells in vitro.

    Science.gov (United States)

    Wang, Chengfeng; Liang, Qinchuan; Chen, Guangming; Jing, Junjie; Wang, Shousen

    2015-01-01

    Medulloblastoma is the most common malignant pediatric brain tumor in children. GPR137 is a ubiquitously expressed gene in the central nervous system. It has been reported that GPR137 modulates malignant proliferation of glioma cells. However, the relationship between GPR137 and medulloblastoma is still unknown. In this study, we knocked down GPR137 in the medulloblastoma cell line Daoy via a lentivirus-based RNA interference system to explore its role in medulloblastoma. Functional analyses showed that cell proliferation and colony formation were obviously restrained in Daoy cells after GPR137 knockdown. Furthermore, knockdown of GPR137 in Daoy cells led to a significant increase in cell percentage in the G0/G1 phase but a decrease in the S phase. Additionally, the cell population in the sub-G1 phase, which represents apoptotic cells, was remarkably increased in GPR137 knockdown cells. GPR137 inhibition induced a strong proapoptotic effect in Daoy cells, as confirmed by annexin V-APC/7-AAD double staining. In conclusion, GPR137 knockdown inhibited growth of Daoy medulloblastoma cells via disturbing cell cycle progression and inducing apoptosis. Our investigation suggested that GPR137 could be a potential oncogene in medulloblastoma cells and might serve as a target for the treatment of medulloblastoma. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  8. Medulloblastoma with Atypical Dynamic Imaging Changes: Case Report with Literature Review.

    Science.gov (United States)

    Song, Shuang-Shuang; Wang, Jian-Hong; Fu, Wei-Wei; Li, Ying; Sui, Qing-Lan; Liu, Xue-Jun

    2017-09-01

    We analyzed a case of medulloblastoma with atypical dynamic imaging changes retrospectively to summarize the atypical magnetic resonance imaging (MRI) features of medulloblastoma by reviewing the literature. An atypical case of medulloblastoma in the cerebellar hemisphere confirmed by pathology was analyzed retrospectively, and the literature about it was reviewed. The radiologic findings of the patient were based on 3 examinations. The first examination showed that the cortex of the bilateral cerebellar hemisphere had diffuse nodular thickening, with a high signal on diffusion-weighted imaging and significant enhancement. Contrast enhancement MRI 1 year later showed the signal of cerebellar hemisphere returned to normal but revealed an enhanced nodule. A reexamination 6 months later showed an irregular mass with a high-density shadow in the cerebellar vermis on CT scan. The T2-weighted image revealed multiple degenerative cysts, and the mass had significant enhancement. The radiologic characteristics of atypical medulloblastomas vary in adults and children. Understanding the radiologic characteristics of medulloblastomas, such as MRI features, age of onset, and location of atypical medulloblastomas, can help improve the diagnosis of medulloblastomas. Copyright © 2017. Published by Elsevier Inc.

  9. Transitioning from genotypes to epigenotypes: why the time has come for medulloblastoma epigenomics.

    Science.gov (United States)

    Batora, N V; Sturm, D; Jones, D T W; Kool, M; Pfister, S M; Northcott, P A

    2014-04-04

    Recent advances in genomic technologies have allowed for tremendous progress in our understanding of the biology underlying medulloblastoma, a malignant childhood brain tumor. Consensus molecular subgroups have been put forth by the pediatric neuro-oncology community and next-generation genomic studies have led to an improved description of driver genes and pathways somatically altered in these subgroups. In contrast to the impressive pace at which advances have been made at the level of the medulloblastoma genome, comparable studies of the epigenome have lagged behind. Complementary data yielded from genomic sequencing and copy number profiling have verified frequent targeting of chromatin modifiers in medulloblastoma, highly suggestive of prominent epigenetic deregulation in the disease. Past studies of DNA methylation-dependent gene silencing and microRNA expression analyses further support the concept of medulloblastoma as an epigenetic disease. In this Review, we aim to summarize the key findings of past reports pertaining to medulloblastoma epigenetics as well as recent and ongoing genomic efforts linking somatic alterations of the genome with inferred deregulation of the epigenome. In addition, we predict what is on the horizon for medulloblastoma epigenetics and how aberrant changes in the medulloblastoma epigenome might serve as an attractive target for future therapies. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    Directory of Open Access Journals (Sweden)

    Shah Keerti V

    2005-02-01

    Full Text Available Abstract Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT, and 8 supratentorial primitive neuroectodermal tumors (sPNET using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3 was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.

  11. MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation.

    Science.gov (United States)

    Liu, Hailong; Sun, Qianwen; Sun, Youliang; Zhang, Junping; Yuan, Hongyu; Pang, Shuhuan; Qi, Xueling; Wang, Haoran; Zhang, Mingshan; Zhang, Hongwei; Yu, Chunjiang; Gu, Chunyu

    2017-09-01

    Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK- or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stem-like cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients.Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275-86. ©2017 AACR. ©2017 American Association for Cancer Research.

  12. The genetic landscape of the childhood cancer medulloblastoma

    OpenAIRE

    Parsons, D. Williams; Li, Meng; Zhang, Xiaosong; Jones, Siân; Leary, Rebecca J.; Lin, Jimmy Cheng-Ho; Boca, Simina M.; Carter, Hannah; Samayoa, Josue; Bettegowda, Chetan; Gallia, Gary L.; Jallo, George I.; Binder, Zev A.; Nikolsky, Yuri; Hartigan, James

    2010-01-01

    Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, 5 to 10-fold fewer than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog ...

  13. Tailoring Medulloblastoma Treatment Through Genomics: Making a Change, One Subgroup at a Time.

    Science.gov (United States)

    Holgado, Borja L; Guerreiro Stucklin, Ana; Garzia, Livia; Daniels, Craig; Taylor, Michael D

    2017-08-31

    After more than a decade of genomic studies in medulloblastoma, the time has come to capitalize on the knowledge gained and use it to directly improve patient care. Although metastatic and relapsed disease remain poorly understood, much has changed in how we define medulloblastoma, and it has become evident that with conventional therapies, specific groups of patients are currently under- or overtreated. In this review, we summarize the latest insights into medulloblastoma biology, focusing on how genomics is affecting patient stratification, informing preclinical studies of targeted therapies, and shaping the new generation of clinical trials.

  14. Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, Roshan V. [Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Rapalino, Otto; Caruso, Paul [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-03-01

    Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for

  15. Differential diagnosis of frontal lobe atrophy from chronic subdural hematoma or subdural hygroma on CT in aged patients. Usefulness of CT cisternogram

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Hideaki [Osaka Univ. (Japan). Faculty of Medicine

    1995-02-01

    Metrizamide CT cisternograms (CTC) were performed in order to examine the CSF passage to subarachnoid space, cerebral sulci and Sylvian fissure. The old aged 20 patients (from 63 to 88 years old) with the layer of low density area around bilateral frontal lobe (bi-frontal LDA) in plain CT finding were selected from 2000 aged patients hospitalized in Hanwa-Senboku Hospital. In these 20 patients, it was difficult to differentiate frontal lobe atrophy from the chronic subdural hematoma and subdural hygroma. Conservative therapy was applied in 19 patients for their old age or their complicated diseases. Only 1 patient was operated for subdural hygroma. The 20 patients were investigated in EEGs, severity of dementia, disturbance of consciousness, activity of daily life, their clinical course and prognosis. Only 2 of the 11 patients with type 1 CTC findings (cerebral sulci, Sylvian fissure and bi-frontal LDA were simultaneously enhanced by metrizamide) showed disturbance of consciousness and/or delirium for their serious somatic disorders. All of 6 patients with type 3 CTC findings (only bi-frontal LDA was not enhanced by metrizamide) showed disturbance of consciousness. Three patients with type 2 CTC findings (atypical findings) were reported independently. Subdural disorder elevating intracranial pressure were clarified in the cases with type 3 CTC findings. (author).

  16. Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient

    Science.gov (United States)

    Zhang, Rui; Howell, Rebecca M.; Giebeler, Annelise; Taddei, Phillip J.; Mahajan, Anita; Newhauser, Wayne D.

    2013-02-01

    Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

  17. Platinum microwire for subdural electrocorticography over human neocortex: millimeter-scale spatiotemporal dynamics.

    Science.gov (United States)

    Kellis, Spencer; Greger, Bradley; Hanrahan, Sara; House, Paul; Brown, Richard

    2011-01-01

    Platinum microwires, terminated at regular intervals to form a grid of contacts, were used to record electric potentials at the surface of the cerebral cortex in human subjects. The microwire grids were manufactured commercially with 75 μm platinum wire and 1 mm grid spacing, and are FDA approved. Because of their small size and spacing, these grids could be used to explore the scale of spatiotemporal dynamics in cortical surface potentials. Electrochemical impedance spectroscopy was used to characterize their recording properties and develop a frequency-dependent electrical model of the micro-electrodes. Data recorded from multiple sites in human cortex were analyzed to explore the relationship between linear correlation and separation distance. A model was developed to explore the impact of cerebrospinal fluid on signal spread among electrodes. Spatial variation in the per-electrode performance decoding articulated speech from face-motor and Wernicke's areas of cortex was explored to understand the scale of information processing at the cortex. We conclude that there are important dynamics at the millimeter scale in human subdural electrocorticography which may be important in maximizing the performance of neural prosthetic applications.

  18. Clinicopathological features of medulloblastoma: an overview with an emphasis on molecular biology

    NARCIS (Netherlands)

    de Haas, T. G. K. J.; Kool, M.

    2007-01-01

    Medulloblastoma is a malignant, invasive embryonal tumor of the cerebellum with preferential manifestation in children, predominantly neuronal differentiation and an inherent tendency to metastasize via CSF pathways. In this review we present an overview of the clinicopathological aspects of

  19. Neuroendoscopic Removal of Acute Subdural Hematoma with Contusion: Advantages for Elderly Patients

    Directory of Open Access Journals (Sweden)

    Ryota Tamura

    2016-01-01

    Full Text Available Background. Large craniotomy for acute subdural hematoma is sometimes too invasive. We report good outcomes for two cases of neuroendoscopic evacuation of hematoma and contusion by 1 burr hole surgery. Case Presentation. Both patients arrived by ambulance at our hospital with disturbed consciousness after falling. Case 1 was an 81-year-old man who took antiplatelet drugs for brain infarction. Case 2 was a 73-year-old alcoholic woman. CT scanning showed acute subdural hematoma and frontal contusion in both cases. In the acute stage, glycerol was administered to reduce edema; CTs after 48 and 72 hours showed an increase of subdural hematoma and massive contusion of the frontal lobe. Disturbed consciousness steadily deteriorated. The subdural hematoma and contusion were removed as soon as possible by neuroendoscopy under local anesthesia, because neither patient was a good candidate for large craniotomy considering age and past history. 40%~70% of the hematoma was removed, and the consciousness level improved. Conclusion. Neuroendoscopic removal of acute subdural hematoma and contusion has advantages and disadvantages. For patients with underlying medical issues or other risk factors, it is likely to be effective.

  20. MRI findings in spinal subdural and epidural hematomas

    Energy Technology Data Exchange (ETDEWEB)

    Braun, Petra [Department of Radiology, Hospital La Plana, Ctra. De Vila-real a Borriana km. 0.5, 12540 Vila-real (Castello) (Spain)], E-mail: PetraBraun@gmx.de; Kazmi, Khuram [Department of Radiology, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States); Nogues-Melendez, Pablo; Mas-Estelles, Fernando; Aparici-Robles, Fernando [Department of Radiology, La Fe Hospital, Avenida Campanar, 21, 46009 Valencia (Spain)

    2007-10-15

    Background: Spinal hematomas are rare entities that can be the cause of an acute spinal cord compression syndrome. Therefore, an early diagnosis is of great importance. Patients and Methods: From 2001 to 2005 seven patients with intense back pain and/or acute progressive neurological deficit were studied via 1.5 T MRI (in axial and sagittal T1- and T2-weighted sequences). Follow-up MRI was obtained in six patients. Results: Four patients showed the MRI features of a hyperacute spinal hematoma (two spinal subdural hematoma [SSH] and two spinal epidural hematoma [SEH]), isointense to the spinal cord on T1- and hyperintense on T2-weighted sequences. One patient had an early subacute SEH manifest as heterogeneous signal intensity with areas of high signal intensity on T1- and T2-weighted images. Another patient had a late subacute SSH with high signal intensity on T1- and T2-weighted sequences. The final patient had a SEH in the late chronic phase being hypointense on T1- and T2-weighted sequences. Discussion: MRI is valuable in diagnosing the presence, location and extent of spinal hematomas. Hyperacute spinal hematoma and the differentiation between SSH and SEH are particular diagnostic challenges. In addition, MRI is an important tool in the follow-up in patients with conservative treatment.

  1. Retroocular and Subdural Hemorrhage or Hemosiderin Deposits in Pediatric Autopsies.

    Science.gov (United States)

    Del Bigio, Marc R; Phillips, Susan M

    2017-04-01

    The presence of hemosiderin in the optic nerve sheath and/or retina is sometimes used to estimate the timing of injury in infants or children with suspected non-accidental head trauma. To determine the prevalence of hemosiderin in deaths not associated with trauma, we performed a prospective study of retroocular orbital tissue, cranial convexity, and cervical spinal cord dura mater in infants and children hemosiderin within the orbital fat, ocular muscles, and parasagittal cranial and/or cervical spinal subdural compartment. This bleeding is likely a consequence of the birth process. None had evidence of hemorrhage within the optic nerve sheath. Premature birth was less likely associated with orbital tissue hemorrhage. Caesarean section birth (mainly nonelective) was not associated with lower prevalence. Residual hemosiderin was identifiable up to 36 weeks postnatal age, suggesting gradual disappearance after birth. Cardiopulmonary resuscitation (performed in the majority of cases) was not associated with acute hemorrhage. In 9 traumatic deaths, 6 had blood and/or hemosiderin within the optic nerve sheath. Knowledge of the potential presence and resolution of hemosiderin in these locations is important for medicolegal interpretation of childhood deaths associated with head or brain injury. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  2. The Molecular Classification of Medulloblastoma: Driving the next generation clinical trials

    Science.gov (United States)

    Leary, Sarah E. S.; Olson, James M.

    2012-01-01

    Purpose of Review Most children diagnosed with cancer today are expected to be cured. Medulloblastoma, the most common pediatric malignant brain tumor, is an example of a disease that has benefitted from advances in diagnostic imaging, surgical techniques, radiation therapy and combination chemotherapy over the past decades. An incurable disease 50 years ago, approximately 70% of children with medulloblastoma are now cured of their disease. However, the pace of increasing the cure rate has slowed over the past two decades, and we have likely reached the maximal benefit that can be achieved with cytotoxic therapy and clinical risk stratification. Long-term toxicity of therapy also remains significant. To increase cure rates and decrease long-term toxicity, there is great interest in incorporating biologic “targeted” therapy into treatment of medulloblastoma, but this will require a paradigm shift in how we classify and study disease. Recent Findings Using genome-based high-throughput analytic techniques, several groups have independently reported methods of molecular classification of medulloblastoma within the past year. This has resulted in a working consensus to view medulloblastoma as four molecular subtypes including WNT pathway subtype, SHH pathway subtype, and two less well-defined subtypes, Group C and Group D. Summary Novel classification and risk stratification based on biologic subtypes of disease will form the basis of further study in medulloblastoma, and identify specific subtypes which warrant greater research focus. PMID:22189395

  3. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    Science.gov (United States)

    2017-10-23

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  4. Spontaneous intracranial hypotension with bilateral subdural hemorrhage: Is conservative management adequate?

    Directory of Open Access Journals (Sweden)

    Mohammed Tauqeer Ahmad

    2013-01-01

    Full Text Available The aim of this study is to report a case of spontaneous intracranial hypotension complicated by bilateral subdural hemorrhage that resolved with conservative management. A young male presented with severe orthostatic headache associated with dizziness, neck pain and diplopia. Brain imaging revealed characteristic pachymeningeal enhancement and bilateral subdural hemorrhage. Radionuclide cisternography confirmed the Cerebrospinal fluid leak at the cervical 5 and cervical 6 vertebral level. He had clinical and radiological resolution with bed rest, hydration and analgesics and has remained symptom free since then. Spontaneous intracranial hypotension may be complicated by bilateral subdural hemorrhage. A conservative treatment approach is a viable option, as it may help improve the clinical and radiological outcome, especially when interventional facilities are not available.

  5. Clinical Observation of Treatment of Chronic Subdural Hematoma With Novel Double Needle Minimally Invasive Aspiration Technology.

    Science.gov (United States)

    Wan, Yi; Fei, Xifeng; Jiang, Dongyi; Chen, Hanchun; Shi, Lei; Wang, Zhimin

    2017-05-01

    The aim of the present study was to explore the clinical effects, including the prevention of complications, of the treatment of chronic subdural hematoma with double needle aspiration. The clinical data of 31 patients with chronic subdural hematoma treated by double YL-1 needle double skull drilling and 31 controls treated by traditional drilling and drainage were analyzed retrospectively. In the YL-1 needle group, only 1 patient was with hematoma recurrence, 1 patient was with intracranial pneumocephalus, and the remaining patients who were followed up for 3 months achieved a clinical cure. In the traditional drilling and drainage group, 13 patients were with hematoma recurrence within 3 months after the operation and 7 patients were with postoperative intracranial pneumocephalus. The method of double YL-1 needle is better than the traditional drilling and drainage method for the treatment of chronic subdural hematoma because it reduces the postoperative recurrence rate and complications.

  6. Multifocal subdural hematomas as the presenting sign of acquired hemophilia A: a case report.

    Science.gov (United States)

    Burish, Mark J; Aysenne, Aimee; Singh, Vineeta

    2014-03-08

    Acquired hemophilia A (AHA) is a rare coagulopathy linked to a variety of etiologies including autoimmune diseases, neoplasms, diabetes, respiratory diseases, and the post-partum state. While bleeding in AHA is often seen in mucocutaneous or intramuscular locations, intracranial and intraspinal bleeds are exceedingly rare. We report an unusual case of spontaneous multifocal subdural hematomas in a 25 year old Asian woman with lupus who presented with headache and backache, and was found to have an elevated partial thromboplastin time (PTT) level and new diagnosis of AHA. Subdural hematomas as the initial sign of AHA are all but unknown in the medical literature. We bring this entity to the attention of the neurology community because lumbar puncture and/or conventional angiogram are often indicated in the work-up of idiopathic multifocal subdural hematomas, but may be dangerous in patients with AHA.

  7. Recurrence of Subdural Haematoma in a Population-Based Cohort - Risks and Predictive Factors.

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    Linnea Schmidt

    Full Text Available To estimate the risks of and identify predictors for recurrent subdural haematoma in surgically and conservatively treated patients.The cohort comprised all individuals diagnosed with a first-time subdural hematoma in Denmark 1996-2011. Information on potential predictors was retrieved from the Danish health registers. Cumulative recurrence risks were estimated using the Aalen-Johansen estimator. Rate ratios (RR were estimated using Poisson regression.Among 10,158 individuals with a subdural hematoma, 1,555 had a recurrent event. The cumulative risk of recurrent subdural hematoma was 9% at 4 weeks after the primary bleeding, increasing to and stabilising at 14% after one year. Predictors associated with recurrence were: Male sex (RR 1.60, 95% CI:1.43-1.80, older age (>70 years compared to 20-49 years; RR 1.41, 95% CI: 1.21-1.65, alcohol addiction (RR 1.20, 95% CI:1.04-1.37, surgical treatment (RR 1.76, 95% CI:1.58-1.96, trauma diagnoses (RR 1.14, 95% CI:1.03-1.27, and diabetes mellitus (RR 1.40, 95% CI:1.11-1.74. Out of a selected combination of risk factors, the highest cumulative 1-year recurrence risks for subdural hematoma of 25% (compared to 14% for all patients was found in surgically treated males with diabetes mellitus.The recurrence risk of subdural hematoma is largely limited to the first year. Patient characteristics including co-morbidities greatly influence the recurrence risk of SDH, suggesting that individualized prognostic guidance and follow-up is needed.

  8. Spontaneous subdural hematoma of the thoracolumbar region with massive recurrent bleed

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    Cincu Rafael

    2009-01-01

    Full Text Available Spinal subdural hematoma is a rare disorder and can be caused by abnormalities of coagulation, blood dyscrasias, lumbar puncture, trauma, underlying neoplasm, and arteriovenous malformation. We discuss an unusual case of an elderly woman who presented with spontaneous spinal subdural hematoma and developed massive rebleeding on the third day following initial evacuation of hematoma. This case illustrates that a patient with routine normal coagulation profile and adequate hemostasis can still harbor platelet dysfunction (in present case due to polycythemia and later on can manifest as rebleeding and neurological deterioration.

  9. Acquired Hemophilia A with a Rare Presentation of Acute Subdural Hematoma

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    Yoshihide Sehara

    2015-01-01

    Full Text Available An 80-year-old man was admitted for acute subdural hematoma caused by a mild brain injury. His coagulation test showed an isolated prolongation of activated partial thromboplastin time (aPTT. Though the subdural hematoma did not progress, oozing bleed from the wound of tracheostomy continued. Failure of correction on aPTT mixing test supported the presence of an inhibitor to a coagulation factor. Once the diagnosis of acquired hemophilia A (AHA was made, steroid therapy was performed, which leads him to complete remission of AHA. Isolated prolongation of aPTT can be the key to diagnose a rare coagulopathy, such as AHA.

  10. Incidence of late endocrine dysfunction following irradiation for childhood medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Abayomi, O.K.; Sadeghi-Nejad, A.

    1986-06-01

    A retrospective analysis of treatment in 20 patients who had received post-operative radiotherapy for medulloblastoma between 1969 and 1977 was completed. The patients were followed for a minimum of 60 months. Eleven patients survived for 5 or more years after treatment. The patients received 3600 cGy to the whole brain. The posterior fossa received 5600 cGY and the spinal axis 3600 cGY. Eight of eleven patients developed growth impairment; 6 of 7 patients had growth hormone deficiency. Since all endocrine gland failures are amenable to therapy, early attention to patients' growth rate and detection of hypothalamic-pituitary failure, would be of benefit to longterm survivors.

  11. [Therapeutic outcomes of medulloblastoma in Casablanca from 2000 to 2012].

    Science.gov (United States)

    Elbachiri, M; Dao, A; Jabir, H; Sahraoui, S; Taleb, A; Bouchbika, Z; Benchakroun, N; Jouhadi, H; Tawfiq, N; Benider, A

    2015-12-01

    To describe the therapeutic results, with the aim to contribute to improving the care of patients with medulloblastoma. A retrospective study of 69 cases of medulloblastoma collected in the university hospital Ibn Rochd of Casablanca between 2000 and 2012. Fifty-three children with an average age of 9 years and 16 adults with an average age of 32.4 years were included in the study. Thirty-seven children and eight adults suffered from a high-risk tumour. The radiotherapy was received by all patients with a mean dose of 36 Gy to the whole brain and 54 Gy in the posterior fossa. All patients in the paediatric group and 10 patients in the adult group received concomitant chemotherapy, 44 children and four adults received adjuvant chemotherapy. Tumour recurrence was observed in 17 children after a mean follow-up period of 38 months. These recurrences were observed in five adults after a mean follow-up period of 42 months. The posterior fossa was the main site of relapses. Overall survival was 77.7% for the children and 61% for the adults. Overall survival was better (70% versus 25%) when the interval between radiotherapy and surgery was less than 40 days in the paediatric group. The recurrence rate was significantly higher for the high-risk group: 41% versus 13% for the standard risk. In the adult group, overall survival differences according to the risk group were significant (100% for the standard risk versus 37.5% for the high risk). The overall survival and recurrences rate obtained are encouraging. The risk group and time between surgery and radiotherapy were prognostic factors with significant impact on survival depending on the age group. We recommend reducing these times to improve therapeutic results. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  12. In vitro Natural Killer cell immunotherapy for medulloblastoma

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    Lucia eFernandez

    2013-04-01

    Full Text Available How the immune system attacks medulloblastoma (MB tumours effectively is unclear, although natural killer (NK cells play an important role in immune defence against tumour cells. Interactions between receptors on NK cells and ligands expressed by tumour cells are critical for tumour control by immunotherapy. In this study, we analysed tumour samples from 54 MB patients for expression of major histocompatibility complex class I-related chains A (MICA and UL16 binding protein (ULPB-2, which are ligands for the NK group 2 member D activatory receptor (NKG2D. The percentage of MICA and ULBP-2 positive cells was higher than 25% in 68% and 6% of MB patients, respectively. A moderate-high intensity of MICA cytoplasmic staining was observed in 46% MB patients and weak ULBP-2 staining was observed in 8% MB patients. No correlation between MICA/ULBP-2 expression and patient outcome was found. We observed that HTB-186, a medulloblastoma cell line, was moderately resistant to NK cell cytotoxicity in vitro. Blocking MICA/ULBP-2 on HTB-186, and NKG2D receptor on NK cells increased resistance to NK cell lysis in vitro. However, HLA class I blocking on HTB-186 and overnight incubation with IL-15 stimulated NK cells efficiently to kill tumour cells in vitro. We conclude that although NKG2D/MICA-ULBP-2 interactions have a role in NK cell cytotoxicity against MB, high expression of HLA class I can protect MB from NK cell cytotoxicity. Even so, our in vitro data indicate that if NK cells are appropriately stimulated, they may have the potential to target MB in vivo.

  13. The KDM1A histone demethylase is a promising new target for the epigenetic therapy of medulloblastoma

    Science.gov (United States)

    2013-01-01

    Background Medulloblastoma is a leading cause of childhood cancer-related deaths. Current aggressive treatments frequently lead to cognitive and neurological disabilities in survivors. Novel targeted therapies are required to improve outcome in high-risk medulloblastoma patients and quality of life of survivors. Targeting enzymes controlling epigenetic alterations is a promising approach recently bolstered by the identification of mutations in histone demethylating enzymes in medulloblastoma sequencing efforts. Hypomethylation of lysine 4 in histone 3 (H3K4) is also associated with a dismal prognosis for medulloblastoma patients. Functional characterization of important epigenetic key regulators is urgently needed. Results We examined the role of the H3K4 modifying enzyme, KDM1A, in medulloblastoma, an enzyme also associated with malignant progression in the closely related tumor, neuroblastoma. Re-analysis of gene expression data and immunohistochemistry of tissue microarrays of human medulloblastomas showed strong KDM1A overexpression in the majority of tumors throughout all molecular subgroups. Interestingly, KDM1A knockdown in medulloblastoma cell lines not only induced apoptosis and suppressed proliferation, but also impaired migratory capacity. Further analyses revealed bone morphogenetic protein 2 (BMP2) as a major KDM1A target gene. BMP2 is known to be involved in development and differentiation of granule neuron precursor cells (GNCPs), one potential cell of origin for medulloblastoma. Treating medulloblastoma cells with the specific KDM1A inhibitor, NCL-1, significantly inhibited growth in vitro. Conclusion We provide the first evidence that a histone demethylase is functionally involved in the regulation of the malignant phenotype of medulloblastoma cells, and lay a foundation for future evaluation of KDM1A-inihibiting therapies in combating medulloblastoma. PMID:24252778

  14. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples.

    Science.gov (United States)

    Northcott, Paul A; Shih, David J H; Remke, Marc; Cho, Yoon-Jae; Kool, Marcel; Hawkins, Cynthia; Eberhart, Charles G; Dubuc, Adrian; Guettouche, Toumy; Cardentey, Yoslayma; Bouffet, Eric; Pomeroy, Scott L; Marra, Marco; Malkin, David; Rutka, James T; Korshunov, Andrey; Pfister, Stefan; Taylor, Michael D

    2012-04-01

    The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence of at least four unique molecular subgroups that exhibit distinct genetic, transcriptional, demographic, and clinical features. Assignment of molecular subgroup through routine profiling of high-quality RNA on expression microarrays is likely impractical in the clinical setting. The planning and execution of medulloblastoma clinical trials that stratify by subgroup, or which are targeted to a specific subgroup requires technologies that can be economically, rapidly, reliably, and reproducibly applied to formalin-fixed paraffin embedded (FFPE) specimens. In the current study, we have developed an assay that accurately measures the expression level of 22 medulloblastoma subgroup-specific signature genes (CodeSet) using nanoString nCounter Technology. Comparison of the nanoString assay with Affymetrix expression array data on a training series of 101 medulloblastomas of known subgroup demonstrated a high concordance (Pearson correlation r = 0.86). The assay was validated on a second set of 130 non-overlapping medulloblastomas of known subgroup, correctly assigning 98% (127/130) of tumors to the appropriate subgroup. Reproducibility was demonstrated by repeating the assay in three independent laboratories in Canada, the United States, and Switzerland. Finally, the nanoString assay could confidently predict subgroup in 88% of recent FFPE cases, of which 100% had accurate subgroup assignment. We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials.

  15. Hematoma subdural agudo traumático: estudo de 110 pacientes Acute traumatic subdural haematomas: study of 110 cases

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    Nicandro de Figueiredo Neto

    1996-06-01

    Full Text Available Apresentamos uma série consecutiva de 110 pacientes com hematoma subdural agudo traumático (HSDA admitidos no serviço de emergência do HBDF no período de 1°-janeiro a 1°-dezembro-1994. Todos os pacientes foram atendidos de acordo com o mesmo protocolo. Houve predominância do sexo masculino (79%, com idade variando entre 14 e 70 anos, sendo os atropelamentos (34% e os acidentes automobilísticos (20% as causas mais comuns. A maioria dos pacientes (85,7% foi admitida muito grave, com 8 pontos ou menos na Escala de Coma Glasgow (ECG, o que influenciou diretamente na mortalidade. A tomografia computadorizada de crânio foi o exame diagnóstico de escolha que mostrou serem as contusões e o inchaço cerebral ("swelling" as lesões intracranianas associadas mais freqüentes. A cirurgia foi realizada em 45,1% dos pacientes, e, em sua maioria, através de craniotomia fronto-têmporo-parietal ampla, com drenagem do hematoma, seguida de plástica da dura-mater. Em 54,9% as condições clínicas não permitiram a realização da cirurgia; neste grupo, cerca de 69,6% estavam em coma profundo à admissão, com 3 pontos na ECG. A letalidade cirúrgica foi de 61,2% e esteve diretamente relacionada à condição clínica inicial e à idade do paciente. A letalidade, incluindo todos os pacientes cirúrgicos e não cirúrgicos com HSDA, mesmo aqueles admitidos já com sinais de falência de tronco cerebral, foi de 79,5%. Além destes pacientes que faleceram, cerca de 7% evoluíram sem seqüelas ou com seqüelas mínimas; outros 11,4% com seqüelas de moderadas a paves e 2,1 % permaneceram em estado vegetativo persistente. Nossos dados estão de acordo com os da literatura no que se refere a elevada taxa de morbidade e mortalidade dos pacientes com HSDA.We report a series of 110 patients with acute traumatic subdural hematoma (ASDH admitted at HBDF emergency within 1994 (January Is1 to December PJ.All patients were treated according to the same protocol

  16. Role of Subdural Electrocorticography in Prediction of Long-Term Seizure Outcome in Epilepsy Surgery

    Science.gov (United States)

    Asano, Eishi; Juhasz, Csaba; Shah, Aashit; Sood, Sandeep; Chugani, Harry T.

    2009-01-01

    Since prediction of long-term seizure outcome using preoperative diagnostic modalities remains suboptimal in epilepsy surgery, we evaluated whether interictal spike frequency measures obtained from extraoperative subdural electrocorticography (ECoG) recording could predict long-term seizure outcome. This study included 61 young patients (age…

  17. Subdural haematoma complicating shunting for normal pressure hydrocephalus in the setting of concomitant antiplatelet medication

    DEFF Research Database (Denmark)

    Birkeland, Peter; Lauritsen, Jens; Poulsen, Frantz Rom

    2016-01-01

    OBJECTIVE: To report on the occurrence and management of subdural haematoma after shunt implantation for normal pressure hydrocephalus and to determine the risk of recurrence in the setting of antiplatelet medication. METHODS: From a consecutive series of 80 patients implanted with a cerebrospinal...

  18. Giant hemicranial calcified subdural empyema--unusual complication following ventriculoperitoneal shunt insertion.

    Science.gov (United States)

    Kasliwal, Manish K; Sinha, Sumit; Kumar, Rajinder; Sharma, Bhawani S

    2009-06-01

    The authors describe an extremely unusual case of a giant hemicranial subdural empyema occurring nine years after insertion of a venticuloperitoneal shunt. Though the empyema was evacuated, the child suffered significant morbidity and remained hemiparetic. The present case highlights the delayed morbidity following a ventriculoperitoneal shunt insertion and the need of prolonged and regular follow up in children who have undergone this procedure.

  19. The subdural space of the spine: A lymphatic sink? Myodil's last message.

    Science.gov (United States)

    Hugh, Alan E

    2010-10-01

    Following the radiological study of a large number of myelograms, starting over 50 years ago when the only clinical contrast medium available to show the contents of the spinal canal was an iodized oil, the author has collected a number of examples where the oil was inadvertently injected into the subdural area, rather than the intended subarachnoid space. By taking follow-up films at various intervals following the inadvertent injection, it has been possible to study the extent to which the subdural space could become visualized from a lumbar injection, the contrast medium sometimes passing to the top of the cervical region and the lower part of the sacrum. Also, the contrast passed outward along the peri-neural lymphatic sheaths or spaces of the issuing spinal nerves, where it might remain for months, and under the influence of gravity it could extend for a considerable way. It also passed into abdominal and thoracic lymph vessels and nodes. Considering the morphology, predictability, and ease with which the demonstrated subdural space fills, the author concludes that the subdural region is a true and functionally significant "space," and an important conduit or functional part of the body's lymphatic system. He also considers that it has implications for the spread or dissemination of various organisms, substances or pathological conditions, as well as being part of the normal conduit for reabsorption of CSF with implications for hydrocephalus, and with potential for misplacement of spinal anaesthetic agents. Copyright © 2010 Wiley-Liss, Inc.

  20. Chronic subdural hematoma pathophysiology: a unifying theory for a dynamic process.

    Science.gov (United States)

    Cecchini, Giulio

    2017-10-01

    Chronic subdural hematoma pathophysiology has been extensively studied and discussed. In the last decades, optic and electron microscope observations have successfully described its histopathology and the ultrastructure of internal membranes. Moreover, recent biochemical studies have identified a number of important pathways involved in its development and evolution. Our aim was to review recent literature regarding histopathology, ultrastructure and biochemichal pathways and supply a unifying theory about chronic subdural hematoma pathophysiology. The starting point of chronic subdural hematoma is a mechanical injury. The evolution of the pathology is due to the exclusive anatomy of the dura-arachnoid interface. This is a mechanically weak layer. Fibroblasts contained in this region produce an inflammatory reaction with neoangiogenesis and fibrinolysis. Biochemical pathways involved in these reactions is complex and could contain a number of pharmacological targets. The hematoma evolves in different stages thus recent outlooks consider chronic subdural hematoma as a dynamic process. One of the key points for a good outcome and a low recurrence rate may be the timing of the surgical treatment in relation of hematoma natural history. Surgery performed during active inflammatory stages may be less effective in terms of clinical outcome and recurrence rate.

  1. Arachnoid Membrane Suturing for Prevention of Subdural Fluid Collection in Extracranial-intracranial Bypass Surgery.

    Science.gov (United States)

    Kim, Gun Woo; Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik; Jang, Jae Won; Seo, Bo Ra; Lee, Jung Kil; Kim, Jae Hyoo; Kim, Soo Han

    2014-06-01

    Water-tight closure of the dura in extracranial-intracranial (EC-IC) bypass is impossible because the superficial temporal artery (STA) must run through the dural defect. Consequently, subdural hygroma and subcutaneous cerebrospinal fluid (CSF) collection frequently occur postoperatively. To reduce these complications, we prospectively performed suturing of the arachnoid membrane after STA-middle cerebral artery (STA-MCA) and evaluated the clinical usefulness. Between Mar. 2005 and Oct. 2010, extracranial-intracranial arterial bypass (EIAB) with/without encephalo-myo-synangiosis was performed in 88 cases (male : female = 53 : 35). As a control group, 51 patients (57 sides) underwent conventional bypass surgery without closure of the arachnoid membrane. Postoperative computed tomography (CT) scan was performed twice in three days and seven days later, respectively, for evaluation of the presence of subdural fluid collection and other mass lesions. The surgical result was excellent, with no newly developing ischemic event until recent follow-up. The additional time needed for arachnoid suture was five to ten minutes, when three to eight sutures were required. Post-operative subdural fluid collection was not seen on follow-up computed tomography scans in all patients. Arachnoid suturing is simple, safe, and effective for prevention of subdural fluid collection in EC-IC bypass surgery, especially the vulnerable ischemic hemisphere.

  2. Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia.

    Science.gov (United States)

    Miyao, Masashi; Abiru, Hitoshi; Ozeki, Munetaka; Kotani, Hirokazu; Tsuruyama, Tatsuaki; Kobayashi, Naho; Omae, Tadaki; Osamura, Toshio; Tamaki, Keiji

    2012-09-10

    Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Subdural hematomas: glutaric aciduria type 1 or abusive head trauma? A systematic review

    NARCIS (Netherlands)

    Vester, Marloes E. M.; Bilo, Rob A. C.; Karst, Wouter A.; Daams, Joost G.; Duijst, Wilma L. J. M.; van Rijn, Rick R.

    2015-01-01

    Glutaric aciduria type 1 (GA1) is a rare metabolic disorder of glutaryl-CoA-dehydrogenase enzyme deficiency. Children with GA1 are reported to be predisposed to subdural hematoma (SDH) development due to stretching of cortical veins secondary to cerebral atrophy and expansion of CSF spaces.

  4. Medulloblastoma in an Adult With Late Extraneural Metastases to the Mediastinum

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    Abhimanyu Ghose MD

    2014-04-01

    Full Text Available Background. Medulloblastoma, although the most common brain tumor of childhood, is exceedingly rare in adults. These tumors have a propensity for local recurrence and to metastasize along the leptomeninges; however, extraneural metastases are very rare and typically occur in the bone or bone marrow. We have not come across any case in literature of medulloblastoma with mediastinal metastases in an adult. Case Presentation. We report a case of medulloblastoma in a 38-year-old lady who was treated with surgery followed by craniospinal radiation. Ten years later she presented with hoarseness from true vocal cord paralysis. She was diagnosed to have infiltrating metastases of her medulloblastoma to the mediastinum, which was confirmed by biopsy. There was no local recurrence. This was treated with chemotherapy followed by stem cell rescue, and she remained progression free for 2 years. Conclusion. Medulloblastomas are rare in adults and can present with late extraneural metastases following treatment. Although most common reported sites are bone and bone marrow, late metastases to other unexpected areas like the mediastinum are possible too and warrant awareness. This can be treated with chemotherapy followed by high-dose chemotherapy and stem cell rescue in a young patient with good performance status.

  5. Update on the integrated histopathological and genetic classification of medulloblastoma - a practical diagnostic guideline.

    Science.gov (United States)

    Pietsch, Torsten; Haberler, Christine

    The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component comprises the four entities WNT-activated, SHH-activated and TP53 wildtype, SHH-activated and TP53 mutant, or non-WNT/non-SHH medulloblastoma. Robust and validated methods are available to allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification, and for differential diagnostic purposes. A combination of immunohistochemical markers including β-catenin, Yap1, p75-NGFR, Otx2, and p53, in combination with targeted sequencing and copy number assessment such as FISH analysis for MYC genes allows a precise assignment of patients for risk-adapted stratification. It also allows comparison to results of study cohorts in the past and provides a robust basis for further treatment refinement.
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  6. Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma

    Science.gov (United States)

    Snuderl, Matija; Batista, Ana; Kirkpatrick, Nathaniel D.; de Almodovar, Carmen Ruiz; Riedemann, Lars; Walsh, Elisa C.; Anolik, Rachel; Huang, Yuhui; Martin, John D.; Kamoun, Walid; Knevels, Ellen; Schmidt, Thomas; Farrar, Christian T.; Vakoc, Benjamin J.; Mohan, Nishant; Chung, Euiheon; Roberge, Sylvie; Peterson, Teresa; Bais, Carlos; Zhelyazkova, Boryana H.; Yip, Stephen; Hasselblatt, Martin; Rossig, Claudia; Niemeyer, Elisabeth; Ferrara, Napoleone; Klagsbrun, Michael; Duda, Dan G.; Fukumura, Dai; Xu, Lei; Carmeliet, Peter; Jain, Rakesh K.

    2013-01-01

    SUMMARY Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastases, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1—and not vascular endothelial growth factor receptor 1 (VEGFR1)—to promote tumor cell survival. This critical tumor-stroma interaction—mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes—supports the development of therapies targeting PlGF/Nrp1 pathway. PMID:23452854

  7. A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer.

    Science.gov (United States)

    Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther

    2016-06-14

    Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.

  8. Drain Insertion in Chronic Subdural Hematoma: An International Survey of Practice.

    Science.gov (United States)

    Soleman, Jehuda; Kamenova, Maria; Lutz, Katharina; Guzman, Raphael; Fandino, Javier; Mariani, Luigi

    2017-08-01

    To investigate whether, after the publication of grade I evidence that it reduces recurrence rates, the practice of drain insertion after burr-hole drainage of chronic subdural hematoma has changed. Further, we aimed to document various practice modalities concerning the insertion of a drain adopted by neurosurgeons internationally. We administered a survey to neurosurgeons worldwide with questions relating to the surgical treatment of chronic subdural hematoma, with an emphasis on their practices concerning the use of a drain. The preferred surgical technique was burr-hole drainage (89%). Most surgeons prefer to place a drain (80%), whereas in 56% of the cases the reason for not placing a drain was brain expansion after evacuation. Subdural drains are placed by 50% and subperiosteal drains by 27% of the responders, whereas 23% place primarily a subdural drain if possible and otherwise a subperiosteal drain. Three quarters of the responders leave the drain for 48 hours and give prophylactic antibiotic treatment, mostly a single-shot dose intraoperatively (70%). Routine postoperative computed tomography is done by 59% mostly within 24-48 hours after surgery (94%). Adjunct treatment to surgery rarely is used (4%). The publication of grade I evidence in favor of drain use influenced positively this practice worldwide. Some surgeons are still reluctant to insert a drain, especially when the subdural space is narrow after drainage of the hematoma. The insertion of a subperiosteal drain could be a good alternative solution. However, its outcome and efficacy must be evaluated in larger studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Restoration of miR-30a expression inhibits growth, tumorigenicity of medulloblastoma cells accompanied by autophagy inhibition.

    Science.gov (United States)

    Singh, Satishkumar Vishram; Dakhole, Aditi Nigam; Deogharkar, Akash; Kazi, Sadaf; Kshirsagar, Rohan; Goel, Atul; Moiyadi, Aliasgar; Jalali, Rakesh; Sridhar, Epari; Gupta, Tejpal; Shetty, Prakash; Gadewal, Nikhil; Shirsat, Neelam Vishwanath

    2017-09-30

    Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas. MicroRNAs are known to play vital roles in nervous system development as well as in cancer. MicroRNA profiling of medulloblastomas identified miR-30 family members' expression to be downregulated in medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH, Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore, established medulloblastoma cell lines Daoy, D283 and D425 were also found to underexpress miR-30a. Restoration of miR-30a expression using inducible lentiviral vector inhibited proliferation, clonogenic potential and tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a mediator of autophagy. MiR-30a expression was found to downregulate Beclin1 expression and inhibit autophagy in the medulloblastoma cell lines as judged by downregulation of LC3B expression and its turnover upon chloroquine treatment and starvation induced autophagy induction. MiR-30a therefore could serve as a novel therapeutic agent for the effective treatment of medulloblastoma by inhibiting autophagy that is known to play important role in cancer cell growth, survival and malignant behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma

    Science.gov (United States)

    2014-01-01

    Background Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients do poorly with significant morbidity. Methods To identify new molecular targets, we performed an integrated genomic analysis using structural and functional methods. Gene expression profiling in 16 medulloblastoma patient samples and subsequent gene set enrichment analysis indicated that cell cycle-related kinases were associated with disease development. In addition a kinome-wide small interfering RNA (siRNA) screen was performed to identify kinases that, when inhibited, could prevent cell proliferation. The two genome-scale analyses were combined to identify key vulnerabilities in medulloblastoma. The inhibition of one of the identified targets was further investigated using RNAi and a small molecule inhibitor. Results Combining the two analyses revealed that mitosis-related kinases were critical determinants of medulloblastoma cell proliferation. RNA interference (RNAi)-mediated knockdown of WEE1 kinase and other mitotic kinases was sufficient to reduce medulloblastoma cell proliferation. These data prompted us to examine the effects of inhibiting WEE1 by RNAi and by a small molecule inhibitor of WEE1, MK-1775, in medulloblastoma cell lines. MK-1775 inhibited the growth of medulloblastoma cell lines, induced apoptosis and increased DNA damage at nanomolar concentrations. Further, MK-1775 was synergistic with cisplatin in reducing medulloblastoma cell proliferation and resulted in an associated increase in cell death. In vivo MK-1775 suppressed medulloblastoma tumor growth as a single agent. Conclusions Taken together, these findings highlight mitotic kinases and, in particular, WEE1 as a rational therapeutic target for medulloblastoma. PMID:24661910

  11. Association between biomarkers and clinical characteristics in chronic subdural hematoma patients assessed with lasso regression.

    Directory of Open Access Journals (Sweden)

    Are Hugo Pripp

    Full Text Available Chronic subdural hematoma (CSDH is characterized by an "old" encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura. Recognized risk factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data

  12. Inactivation of Ezh2 Upregulates Gfi1 and Drives Aggressive Myc-Driven Group 3 Medulloblastoma.

    Science.gov (United States)

    Vo, BaoHan T; Li, Chunliang; Morgan, Marc A; Theurillat, Ilan; Finkelstein, David; Wright, Shaela; Hyle, Judith; Smith, Stephanie M C; Fan, Yiping; Wang, Yong-Dong; Wu, Gang; Orr, Brent A; Northcott, Paul A; Shilatifard, Ali; Sherr, Charles J; Roussel, Martine F

    2017-03-21

    The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers suppressed by Ezh2 included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor-promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in driving MB progression in primary cerebellar neuronal progenitors. Although negative regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Cauda equina syndrome as the initial presenting clinical feature of medulloblastoma: a case report

    Directory of Open Access Journals (Sweden)

    Al-Otaibi Faisal

    2012-05-01

    Full Text Available Abstract Introduction Medulloblastoma is one of the most common pediatric brain malignancies. The usual presenting clinical features are related to posterior fossa syndrome or/and hydrocephalus. Cauda equina syndrome is a very rare presentation for this disease. Case presentation We describe the case of a three-year-old boy with cauda equina syndrome as the initial presenting clinical feature for medulloblastoma. He was initially diagnosed as having a spinal tumor by magnetic resonance imaging scan. Subsequently, a cranial magnetic resonance imaging scan revealed a posterior fossa tumor with features of dissemination. He had substantial improvement after treatment. This case report is complemented by a literature review related to this unusual presentation. Conclusions Medulloblastoma primarily presenting with cauda equina syndrome is very rare. However, spinal drop metastasis should be considered in the pediatric age group to avoid suboptimal management.

  14. Goldenhar syndrome and medulloblastoma: a coincidental association? The first case report.

    Science.gov (United States)

    Aizenbud, Dror; Shoham, Natasha V; Constantini, Shlomi; Nevo, Neta; Ben Arush, Myriam; Raz, Michal; Rachmiel, Adi; Goldsher, Dorit

    2014-07-01

    Features of Goldenhar syndrome include several craniofacial anomalies of structures derived from the first and second pharyngeal arches, as well as vertebral, cardiac and renal systems abnormalities. In addition, Goldenhar patients were reported to manifest a variety of central nervous system anomalies and several types of neoplasias. The first case of medulloblastoma in a patient with Goldenhar syndrome is presented here. There is no clear association between these two pathologies. We speculate that aberrant events during the migration of neural crest cells in early stages of development could be the basis of an association between medulloblastoma and Goldenhar syndrome. The case history suggests other possible etiological contributing factors to the development of medulloblastoma, such as patient's history of trauma and/or early childhood exposure to ionizing radiation. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  15. Replication stress, DNA damage signalling, and cytomegalovirus infection in human medulloblastomas

    DEFF Research Database (Denmark)

    Bartek, Jiri; Fornara, Olesja; Merchut-Maya, Joanna Maria

    2017-01-01

    of the clinical specimens also showed expression of HCMV immediate early and late proteins, in comparative analyses using three immunohistochemical protocols. Cell culture experiments validated the chronic endogenous replication stress in medulloblastoma cell lines and showed sharply differential, intriguing...... eight established immunohistochemical markers to assess the status of the DDR machinery, we found pronounced endogenous DNA damage signalling (γH2AX marker) and robust constitutive activation of both the ATM-Chk2 and ATR-Chk1 DNA damage checkpoint kinase cascades, yet unexpectedly modest p53 tumour...... responses of normal cells and medulloblastoma cells to HCMV infection, including differential subcellular mislocalization and enhancement of replication stress-related 53BP1 body formation, the latter in cell-non-autonomous manner. Overall, our results strongly indicate that in human medulloblastomas...

  16. The rising root sign: the magnetic resonance appearances of post-operative spinal subdural extra-arachnoid collections

    Energy Technology Data Exchange (ETDEWEB)

    Bharath, A.; Uhiara, O.; Botchu, Rajesh; Davies, A.M.; James, S.L. [The Royal Orthopedic Hospital, Department of Musculoskeletal Radiology, Birmingham (United Kingdom)

    2017-09-15

    We present a case series of symptomatic post-operative spinal subdural extra-arachnoid collections that displace the cauda equina roots anteriorly. This is described as the ''rising root sign''. (orig.)

  17. Acute onset of intracranial subdural hemorrhage five days after spinal anesthesia for knee arthroscopic surgery: a case report

    Directory of Open Access Journals (Sweden)

    Hagino Tetsuo

    2012-03-01

    Full Text Available Abstract Introduction Spinal anesthesia is a widely used general purpose anesthesia. However, serious complications, such as intracranial subdural hemorrhage, can rarely occur. Case presentation We report the case of a 73-year-old Japanese woman who had acute onset of intracranial subdural hemorrhage five days after spinal anesthesia for knee arthroscopic surgery. Conclusion This case highlights the need to pay attention to acute intracranial subdural hemorrhage as a complication after spinal anesthesia. If the headache persists even in a supine position or nausea occurs abruptly, computed tomography or magnetic resonance imaging of the brain should be conducted. An intracranial subdural hematoma may have a serious outcome and is an important differential diagnosis for headache after spinal anesthesia.

  18. Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells.

    Science.gov (United States)

    Pelzl, Lisann; Hosseinzadeh, Zohreh; Al-Maghout, Tamer; Singh, Yogesh; Sahu, Itishri; Bissinger, Rosi; Schmidt, Sebastian; Alkahtani, Saad; Stournaras, Christos; Toulany, Mahmoud; Lang, Florian

    2017-01-01

    Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (Δ[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Clinical characteristics and abandonment and outcome of treatment in 67 Chinese children with medulloblastoma.

    Science.gov (United States)

    Wang, Chen; Yuan, Xiao-Jun; Jiang, Ma-Wei; Wang, Li-Feng

    2016-01-01

    OBJECT The purpose of this study was to explore the clinical features and outcome of medulloblastoma in Chinese children. The authors analyze the reasons that treatment is abandoned and attempt to provide evidence-based recommendations for improving the prognosis of medulloblastoma in this population. METHODS A total of 67 pediatric cases of newly diagnosed medulloblastoma were included in this study. All of the children were treated at Xinhua Hospital between January 2007 and June 2013. The authors retrospectively analyzed the clinical data, treatment modalities, and outcome. The male-to-female ratio was 2:1, and the patients' median age at diagnosis was 51.96 months (range 3.96-168.24 months). The median duration of follow-up was 32 months (range 3-70 months). RESULTS At the most recent follow-up date, 31 patients (46%) were alive, 30 (45%) had died, and 6 (9%) had been lost to follow-up. The estimated 3-year overall survival and progression-free survival, based on Kaplan-Meier analysis, were 55.1% ± 6.4% and 45.6% ± 6.7%, respectively. Univariate analysis showed that standard-risk group (p = 0.009), postoperative radiotherapy (RT) combined with chemotherapy (p medulloblastoma in Chinese children and the outcome in Western children. Based on our data, treatment abandonment was the major cause of therapeutic failure. Parents' misunderstanding of medulloblastoma played a major role in abandonment, followed by financial and transportation difficulties. Establishment of multidisciplinary treatment teams could improve the prognosis of medulloblastoma in Chinese children.

  20. An Unusual Combination of Mirror-Image Dextrocardia with Familial Medulloblastoma: Is There a Histogenetic Relationship?

    Science.gov (United States)

    Ke, Chao; Wang, Jing; Xi, Shaoyan; Li, Kay Ka-Wai; Luo, Junran; Chen, Zhenghe; Wang, Jian; Chen, Zhong-Ping

    2017-11-01

    The occurrence of medulloblastoma in the absence of hereditary syndromes is rare. Dextrocardia with situs inversus is also called mirror-image dextrocardia. A combination of mirror-image dextrocardia with medulloblastoma has not been reported previously. To the best of our knowledge, this is the first report of this rare combination in a family with medulloblastoma. The clinical manifestation, radiographic characteristics, treatment, and outcomes of 3 medulloblastoma cases in 2 cousins and their maternal uncle was described. Tumor samples of the 2 cousins were first examined for histologic subtypes. Total RNA of their tumors was extracted from formalin-fixed and paraffin-embedded samples. Then, expression of 22 subgroup-specific genes and 3 housekeeping genes was analyzed by the NanoString nCounter Analysis System. The posttest data were normalized by NanoStringNorm package for molecular subgroup prediction. The proband remains tumor free and alive up to the latest follow-up. His cousin, who had combined mirror-image dextrocardia with situs inversus, died of anoxia after surgery and his uncle died of tumor 2.5 years after surgery. Medulloblastoma of the 2 cousins was classified as classic and molecular group 4 subtype. The same classic and molecular group 4 subtype of the 2 cousins may suggest a similar genetic predisposition. Involvement of the Otx2 gene dysfunction in both group 4 subtype medulloblastoma and mirror-image dextrocardia with situs inversus points to a possible mechanism that dysfunction of a shared signaling pathway such as Otx2 might be the underlying cause of these 2 conditions in this family. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets.

    Science.gov (United States)

    Sun, Lue; Moritake, Takashi; Ito, Kazuya; Matsumoto, Yoshitaka; Yasui, Hironobu; Nakagawa, Hidehiko; Hirayama, Aki; Inanami, Osamu; Tsuboi, Koji

    2017-01-01

    Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS) production, mitochondria function, oxygen consumption rate (OCR), energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma.

  2. Rapid spontaneous resolution and redistribution of acute subdural hematoma in a patient with chronic alcoholism: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Tsui, Edmund Yik Kong. E-mail: yktsui@hongkong.com; Fai Ma, Ka; Cheung, Yu Keung; Chan, Jimmy Hon Mo; Yuen, Ming Keung

    2000-10-01

    We report a case of a 54-year-old man who had documented traumatic acute subdural hematoma. He suffered from a transient episode of confusion and a follow-up CT scan of brain 6 h after the initial scan showed resolution and redistribution of the subdural hematoma. In this case report, we review the literature for the underlying pathophysiology of this uncommon phenomenon.

  3. Medulloblastoma Presenting With Pure Word Deafness: Report of One Case and Review of Literature

    Directory of Open Access Journals (Sweden)

    Yen-Ting Chou

    2011-10-01

    Full Text Available Pure word deafness (PWD is a rare disorder characterized by impaired verbal comprehension sparing discrimination and recognition of nonverbal sounds with relatively normal spontaneous speech, writing, and reading comprehension. Etiologies of this syndrome are varied, and there are rare reports about brain tumor with PWD in children. We report a case of medulloblastoma presented with PWD in a 7-year-old girl. She visited our outpatient clinic because of English dictation performance deterioration. PWD was diagnosed by the otolaryngologist after examinations. Posterior fossa tumor and obstructive hydrocephalus were shown in the magnetic resonance imaging of the brain. The diagnosis of medulloblastoma was then made by pathology.

  4. The genetic landscape of the childhood cancer medulloblastoma

    Science.gov (United States)

    Parsons, D. Williams; Li, Meng; Zhang, Xiaosong; Jones, Siân; Leary, Rebecca J.; Lin, Jimmy Cheng-Ho; Boca, Simina M.; Carter, Hannah; Samayoa, Josue; Bettegowda, Chetan; Gallia, Gary L.; Jallo, George I.; Binder, Zev A.; Nikolsky, Yuri; Hartigan, James; Smith, Doug R.; Gerhard, Daniela S.; Fults, Daniel W.; VandenBerg, Scott; Berger, Mitchel S.; Marie, Suely Kazue Nagahashi; Shinjo, Sueli Mieko Oba; Clara, Carlos; Phillips, Peter C.; Minturn, Jane E.; Biegel, Jaclyn A.; Judkins, Alexander R.; Resnick, Adam C.; Storm, Phillip B.; Curran, Tom; He, Yiping; Rasheed, B. Ahmed; Friedman, Henry S.; Keir, Stephen T.; McLendon, Roger; Northcott, Paul A.; Taylor, Michael D.; Burger, Peter C.; Riggins, Gregory J.; Karchin, Rachel; Parmigiani, Giovanni; Bigner, Darell D.; Yan, Hai; Papadopoulos, Nick; Vogelstein, Bert; Kinzler, Kenneth W.; Velculescu, Victor E.

    2011-01-01

    Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, 5 to 10-fold fewer than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis. PMID:21163964

  5. Targeted treatment for sonic hedgehog-dependent medulloblastoma

    Science.gov (United States)

    Kieran, Mark W.

    2014-01-01

    Novel treatment options, including targeted therapies, are needed for patients with medulloblastoma (MB), especially for those with high-risk or recurrent/relapsed disease. Four major molecular subgroups of MB have been identified, one of which is characterized by activation of the sonic hedgehog (SHH) pathway. Preclinical data suggest that inhibitors of the hedgehog (Hh) pathway could become valuable treatment options for patients with this subgroup of MB. Indeed, agents targeting the positive regulator of the pathway, smoothened (SMO), have demonstrated efficacy in a subset of patients with SHH MB. However, because of resistance and the presence of mutations downstream of SMO, not all patients with SHH MB respond to SMO inhibitors. The development of agents that target these resistance mechanisms and the potential for their combination with traditional chemotherapy and SHH inhibitors will be discussed. Due to its extensive molecular heterogeneity, the future of MB treatment is in personalized therapy, which may lead to improved efficacy and reduced toxicity. This will include the development of clinically available tests that can efficiently discern the SHH subgroup. The preliminary use of these tests in clinical trials is also discussed herein. PMID:24951114

  6. Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

    Directory of Open Access Journals (Sweden)

    Hourinaz Behesti

    2013-01-01

    BMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers – including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival.

  7. A review of sub acute subdural hematoma (SASDH) with our institutional experience and its management by double barrel technique (DbT): A novel technique

    OpenAIRE

    Tripathy, Soubhagya R.; Swarnakar, Pankaj K.; Mishra, Sanjib; Mishra, Sudhanshu S.; Dhir, Manmath K.; Behera, Sanjay K.; Nath, Pratap C.; Jena, Somnath P.; Mohanta, Itibrata; Das, Deepak; Satapathy, Mani C.; Rout, Sitansu K.; Behera, Bikash R.; Parida, Deepak K.; Rath, Tanushree S.

    2016-01-01

    Background: Subacute subdural hematoma (SASDH) is an entity which is yet to capture the popular imagination among the neurosurgeons. Its management is often equated clinically to that of the chronic subdural hematoma (CSDH). However, their neurological deterioration is usually rapid, which seems to align them with acute subdural hematoma (ASDH). We proceed for their epidemiological evaluation. The advantages of a novel "double barrel technique (DbT)" over the conventional burrhole drainage ar...

  8. Spontaneous acute subdural hematoma contralateral to an arachnoid cyst Hematoma subdural agudo espontâneo contralateral a cisto aracnóideo

    Directory of Open Access Journals (Sweden)

    José Gilberto de Brito Henriques

    2007-12-01

    Full Text Available Arachnoid cysts (AC are extra-cerebral cerebrospinal fluid collections of unknown origin. They correspond to 1% of all intracranial nontraumatic space-occupying lesions and appear more frequently in the middle fossa (50%. More than 25% of these cysts are incidental findings and the majority of patients are asymptomatic. Seizures, intracranial hypertension signs, neurological deficits, macrocrania, developmental delay and bulging of the skull are the main signs and symptoms of the lesion. AC rupture and bleeding are rare, usually occurring in young adults and associated with trauma. The risk of hemorrhage does not exceed 0.04% / year. We describe the case of a ten-year-old boy who presented with acute signs of intracranial hypertension secondary to a spontaneous acute subdural hematoma, contralateral to an AC of the middle fossa. Three factors were significant in this case: signs and symptoms occurred spontaneously; the presence of an acute subdural hematoma exclusively contralateral to the AC; successful outcome of the conservative treatment.Os cistos aracnóideos (CA são coleções liquóricas extra-cerebrais e intra-aracnóideas de origem desconhecida. Correspondem a 1% de todas as lesões expansivas intracranianas não traumáticas e têm nítido predomínio na fossa média (50%. Até 25% destes cistos são achados incidentais sendo que a maioria dos pacientes é assintomática. Crises epilépticas, sinais de hipertensão intracraniana, déficits neurológicos focais, macrocrania, atraso no desenvolvimento e abaulamento da calota craniana são os principais sinais e sintomas da lesão. A ruptura dos CA, assim como seu sangramento, são situações raras, geralmente associadas a traumas e acometem adultos jovens. O risco de hemorragia em pacientes com CA não excede 0,04% ao ano. É descrito caso de paciente de dez anos de idade que subitamente apresentou sinais de hipertensão intracraniana secundários a hematoma subdural agudo espont

  9. Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

    Science.gov (United States)

    2012-01-01

    Background Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. Methods We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Results Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Conclusions Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants

  10. SU-E-T-375: Passive Scattering to Pencil-Beam-Scanning Comparison for Medulloblastoma Proton Therapy: LET Distributions and Radiobiological Implications

    Energy Technology Data Exchange (ETDEWEB)

    Giantsoudi, D; MacDonald, S; Paganetti, H [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2014-06-01

    Purpose: To compare the linear energy transfer (LET) distributions between passive scattering and pencil beam scanning proton radiation therapy techniques for medulloblastoma patients and study the potential radiobiological implications. Methods: A group of medulloblastoma patients, previously treated with passive scattering (PS) proton craniospinal irradiation followed by prosterior fossa or involved field boost, were selected from the patient database of our institution. Using the beam geometry and planning computed tomography (CT) image sets of the original treatment plans, pencil beam scanning (PBS) treatment plans were generated for the cranial treatment for each patient, with average beam spot size of 8mm (sigma in air at isocenter). 3-dimensional dose and LET distributions were calculated by Monte Carlo methods (TOPAS) both for the original passive scattering and new pencil beam scanning treatment plans. LET volume histograms were calculated for the target and OARs and compared for the two delivery methods. Variable RBE weighted dose distributions and volume histograms were also calculated using a variable dose and LET-based model. Results: Better dose conformity was achieved with PBS planning compared to PS, leading to increased dose coverage for the boost target area and decreased average dose to the structures adjacent to it and critical structures outside the whole brain treatment field. LET values for the target were lower for PBS plans. Elevated LET values for OARs close to the boosted target areas were noticed, due to end of range of proton beams falling inside these structures, resulting in higher RBE weighted dose for these structures compared to the clinical RBE value of 1.1. Conclusion: Transitioning from passive scattering to pencil beam scanning proton radiation treatment can be dosimetrically beneficial for medulloblastoma patients. LET–guided treatment planning could contribute to better decision making for these cases, especially for

  11. Recurrence of Subdural Haematoma in a Population-Based Cohort - Risks and Predictive Factors

    DEFF Research Database (Denmark)

    Schmidt, Linnea; Gørtz, Sanne; Wohlfahrt, Jan

    2015-01-01

    % CI:1.04-1.37), surgical treatment (RR 1.76, 95% CI:1.58-1.96), trauma diagnoses (RR 1.14, 95% CI:1.03-1.27), and diabetes mellitus (RR 1.40, 95% CI:1.11-1.74). Out of a selected combination of risk factors, the highest cumulative 1-year recurrence risks for subdural hematoma of 25% (compared to 14...... was retrieved from the Danish health registers. Cumulative recurrence risks were estimated using the Aalen-Johansen estimator. Rate ratios (RR) were estimated using Poisson regression. RESULTS: Among 10,158 individuals with a subdural hematoma, 1,555 had a recurrent event. The cumulative risk of recurrent...

  12. POSTSPINAL INTRACRANIAL SUBDURAL HEMATOMA AND CEREBRAL SINUS THROMBOSIS: REPORT OF A CASE

    Directory of Open Access Journals (Sweden)

    Ali ihsan Uysal

    2013-06-01

    Full Text Available Cerebral venous thrombosis is a rare but a serious complication of spinal anesthesia. It usually occurs in the presence of predisposing factors such as pregnancy, puerperium, use of oral contraceptive drugs, malignancies, thrombocytopenia and the most frequent symptom is headache. Twenty-two years of age, pregnant woman had a complaint of headache after spinal anesthesia for caesarean section and diagnosed as post-dural puncture headache, the treatment was begun. After detecting responsiveness to treatment, radiological imaging procedures were performed and subdural hematoma and transverse sinus thrombosis were detected. In this case report, it was concluded under current literatures that the subdural hematoma and transverse sinus thrombosis should be kept in mind during the diagnosis of post-dural puncture headache. [J Contemp Med 2013; 3(2.000: 116-120

  13. Treatment of a subdural empyema complicated by intracerebral abscess due to Brucella infection

    Directory of Open Access Journals (Sweden)

    J. Zhang

    Full Text Available A 55-year-old male presented with fever, stupor, aphasia, and left hemiparesis. A history of head trauma 3 months before was also reported. Cranial magnetic resonance imaging revealed slight contrast enhancement of lesions under the right frontal skull plate and right frontal lobe. Because of deterioration in nutritional status and intracranial hypertension, the patient was prepared for burr hole surgery. A subdural empyema (SDE recurred after simple drainage. After detection of Brucella species in SDE, craniotomy combined with antibiotic treatment was undertaken. The patient received antibiotic therapy for 6 months (two doses of 2 g ceftriaxone, two doses of 100 mg doxycycline, and 700 mg rifapentine for 6 months that resulted in complete cure of the infection. Thus, it was speculated that the preexisting subdural hematoma was formed after head trauma, which was followed by a hematogenous infection caused by Brucella species.

  14. Subdural Hematoma: A Rare Adverse Complication From Bone-Anchored Hearing Aid Placement.

    Science.gov (United States)

    Amin, Nikul; Aymat-Torrente, Antonio

    2017-03-01

    Bone-anchored hearing aids (BAHA) are bone conduction hearing aids commonly implantated by Ear, Nose, and Throat surgeons. We present the first documented case of a subdural hematoma secondary to primary fixation of a BAHA. We present a 65-year-old male patient undergoing a left sided BAHA for bilateral chronic ear infections and difficulty wearing conventional hearing aids. The procedure was uneventful, however, the patient developed a postoperative large acute left temporoparietal intracerebral hematoma associated with an ipsilateral acute subdural hematoma. This required emergency transfer to the local tertiary neurosurgical center for a left decompressive craniotomy and evacuation of the hematoma. The patient required a prolonged stay on an intensive care unit and was eventually discharged to the community for on-going neurological rehabilitation. This is a rare and devastating complication BAHA surgery. Otologist, general ENT surgeons, and neurosurgeons should be aware of this life-threatening complication of BAHA surgery.

  15. Anatomy and development of the meninges: implications for subdural collections and CSF circulation

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Julie [Penn State Hershey Medical Center, Department of Radiology, Hershey, PA (United States); Squier, Waney [John Radcliffe Hospital, Department of Neuropathology, Oxford (United Kingdom); Eastman, James T. [Lancaster General Hospital, Department of Pathology and Laboratory Medicine, Lancaster, PA (United States)

    2009-03-15

    The dura is traditionally viewed as a supportive fibrous covering of the brain containing the dural venous sinuses but otherwise devoid of vessels and lacking any specific function. However, review of the embryology and anatomy reveals the dura to be a complex, vascularized and innervated structure, not a simple fibrous covering. The dura contains an inner vascular plexus that is larger in the infant than in the adult, and this plexus likely plays a role in CSF absorption. This role could be particularly important in the infant whose arachnoid granulations are not completely developed. Although subdural hemorrhage is frequently traumatic, there are nontraumatic conditions associated with subdural hemorrhage, and the inner dural plexus is a likely source of bleeding in these nontraumatic circumstances. This review outlines the development and age-specific vascularity of the dura and offers an alternative perspective on the role of the dura in homeostasis of the central nervous system. (orig.)

  16. Meningitis and subdural empyema as complication of pterygomandibular space abscess upon tooth extraction.

    Science.gov (United States)

    Cariati, Paolo; Cabello-Serrano, Almudena; Monsalve-Iglesias, Fernando; Roman-Ramos, Maria; Garcia-Medina, Blas

    2016-10-01

    Complication of dental infections might be various and heterogeneous. The most common complications are represented by maxilar celulitis, canine space celulitis, infratemporal space celulitis, temporal celulitis and bacteremia. Among rarest complications we found: sepsis, bacterial endocarditis, mediastinitis, intracranial complications, osteomyelitis, etc. Although dental infections are often considered trivial entities, sometimes they can reach an impressive gravity. In this regard, the present study describes a case of dental infection complicated by meningitis, subdural empiema and cerebral vasculitis. Furthermore, we observed other neurological complications, like thalamic ischemic infarction, during the disease evolution. Noteworthy, these entities were not presented when the patient was admitted to hospital. Therefore, the main aim of this report is to highlight the serious consequences that an infection of dental origin could cause. Key words: Meningitis, subdural empyema, odontogenic infections.

  17. HEMATOMA SUBDURAL EN PACIENTE CON LEUCEMIA MIELODE CRONICA: REPORTE DE CASO

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Lozano-Tangua

    2009-01-01

    Full Text Available El hematoma subdural cronico se define como una colección sanguíneo fibrinoide en el espacio existente entre las meninges duramadre y aracnoides, debido a traumas, infecciones (empiema y meningitis, coagulopatías u otras causas. En este se puede precisar durante la intervención quirúrgica la presencia de cápsula o membranas. Entre las diversas causas de hematoma subdural crónico se encuentra la leucemia mieloide crónica que es un síndrome mieloproliferativo, donde se ve una acentuada proliferación de glóbulos blancos de la serie granulocítica, que infiltran la sangre, médula ósea, cerebro entre otros tejidos. Presentamos brevemente un caso de esta interesante y no infrecuente asociación.

  18. Age related outcome in acute subdural haematoma following traumatic head injury.

    LENUS (Irish Health Repository)

    Hanif, S

    2009-09-01

    Acute subdural haematoma (ASDH) is one of the conditions most strongly associated with severe brain injury. Reports prior to 1980 describe overall mortality rates for acute subdural haematomas (SDH\\'s) ranging from 40% to 90% with poor outcomes observed in all age groups. Recently, improved results have been reported with rapid diagnosis and surgical treatment. The elderly are predisposed to bleeding due to normal cerebral atrophy related to aging, stretching the bridging veins from the dura. Prognosis in ASDH is associated with age, time from injury to treatment, presence of pupillary abnormalities, Glasgow Coma Score (GCS) or motor score on admission, immediate coma or lucid interval, computerized tomography findings (haematoma volume, degree of midline shift, associated intradural lesion, compression of basal cisterns), post-operative intracranial pressure and type of surgery. Advancing age is known to be a determinant of outcome in head injury. We present the results of a retrospective study carried out in Beaumont Hospital, Dublin, Ireland\\'s national neurosurgical centre. The aim of our study was to examine the impact of age on outcome in patients with ASDH following severe head injury. Only cases with acute subdural haematoma requiring surgical evacuation were recruited. Mortality was significantly higher in older patients (50% above 70 years, 25.6% between 40 and 70 years and 26% below 40 years). Overall poor outcome (defined as Glasgow outcome scores 3-5) was also higher in older patients; 74.1% above 70 years, 48% between 40 and 70 years and 30% below 40 years. Poor outcome in traumatic acute subdural haematoma is higher in elderly patients even after surgical intervention.

  19. A STUDY ON MANAGEMENT OF CHRONIC SUBDURAL HAEMATOMA- BURR HOLE EVACUATION AND MINI CRANIOTOMY

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    Nandigama Pratap Kumar

    2016-11-01

    Full Text Available BACKGROUND Chronic SDH is one of the common neurosurgical conditions requiring surgical treatment. The incidence of chronic SDH is 1.7- 18 per 1,00,000 population. The incidence is higher in the elderly patients, i.e. 58 per 1,00,000. Various treatment modalities available for the treatment of chronic SDH indicate that there is no gold standard for the treatment of chronic SDH. Recurrence is the major problem following treatment and can be as high as 30%. Mini craniotomy is one of the surgical options that can offer better view of the subdural space and may allow us to efficiently clear the loculations and haematoma fluid and thereby decreasing the incidence of recurrences and the need for reoperations. Small craniotomies have not been studied well in the literature except for a few publications. In this study, we are comparing mini craniotomy and burr hole evacuation for the treatment of chronic SDH. MATERIALS AND METHODS All the patients with chronic subdural haematoma operated between August 2013 and January 2016. Patients with recurrent SDH on the same side and patients who underwent different procedures on either side (in case of bilateral haematomas were excluded from the study. The patients were operated by two senior surgeons with one surgeon doing burr hole evacuation and another doing mini craniotomy. Preoperative status and postoperative status was analysed. RESULTS All the patients were analysed both preoperatively and postoperatively. In both the groups, most of the patients shown improvement following surgery, but recurrences are more in burr hole group when compared to mini craniotomy. CONCLUSION Mini craniotomy allows better view of the subdural space and better evacuation of chronic subdural haematoma. Cure rate is higher with mini craniotomy compared to burr hole evacuation.

  20. Diagnosis of subdural haematoma by computed axial tomography: use of xenon inhalation for contrast enhancement.

    Science.gov (United States)

    Zilkha, E; Kendall, B E; Loh, L; Hayward, R; Radue, E W; ingram, G S

    1978-01-01

    A subdural haematoma is described in which a definite computed tomographic (CT) scan diagnosis was made only after contrast enhancement had been achieved by the inhalation of xenon. The different types of enhancement obtained with iodide containing contrast media and with xenon are discussed. The use of xenon to obtain further information in conditions which are inadequately elucidated by conventional CT must be balanced against its anaesthetic effects and relatively high cost. Images PMID:650246

  1. Subdural lumbar facet joint fistula secondary to dural tear case report.

    Science.gov (United States)

    Nakashima, Hiroaki; Yukawa, Yasutsugu; Ito, Keigo; Machino, Masaaki; Kato, Fumihiko

    2010-06-01

    A case report. To report a rare complication associated with lumbar decompression surgery. Decompression surgery for lumbar degenerative canal stenosis is one of the most commonly performed spinal procedures. A dural tear is a common troublesome complication of the surgery. Occasionally, dural tear can lead to cerebrospinal fluid (CSF) fistula. However, there is no report of a CSF fistula between the subdural space and a facet joint. A 79-year-old woman underwent lumbar decompression surgery at L3-L5 level. During the surgery, a minimal dural tear was detected although the arachnoid membrane was intact. Because of the absence of CSF leakage and small size of the torn area, repair was not performed. After surgery, she complained of intermittent left buttock pain after ambulation. Her magnetic resonance imaging showed enlarged subdural space and tethering of the dura at L3-L4. CSF aspiration from subdural space was conducted during myelography. However, pain relief was only temporary. CSF fistula between subdural space and facet joint was detected on computed tomographic myelography (CTM). She subsequently underwent second surgery. After separation of the adhesion between the dural tear and the facet joint, CSF leakage was observed. Water-tight sutures, free fat graft, and fibrin glue were applied for repair. She demonstrated complete resolution of her preoperative symptoms at 1 year after surgery. Follow-up magnetic resonance imaging showed no recurrence of the fistula and an adequately decompressed lumbar canal. Computed tomographic myelography was essential to diagnose the rare complication after dural tear. Even in cases of minimal dural tears without arachnoid tear, we suggest repair in order to prevent the rare case of fistula formation.

  2. [Rapid resolution of acute subdural haematoma with significant impact on clinical outcome].

    Science.gov (United States)

    Capion, Tenna; Lilja-Cyron, Alexander; Kelsen, Jesper

    2017-09-04

    A 73-year-old woman was admitted to hospital due to anaemia. She suffered a minor head trauma and deteriorated to deep unconsciousness. A CT revealed an acute subdural haematoma (ASDH). Initially, she was not found to be a candidate for neurosurgical intervention, but within 24 hours her level of consciousness improved dramatically, and a renewed CT showed resolution of the ASDH. She underwent acute craniotomy with good outcome. This illustrates the importance of re-evaluation of patients with intracranial haemorrhage.

  3. Neurological and functional outcomes of subdural hematoma evacuation in patients over 70 years of age

    Directory of Open Access Journals (Sweden)

    Patrick Mulligan

    2013-01-01

    Full Text Available Background: Subdural hematoma (SDH is a common disease entity treated by neurosurgical intervention. Although the incidence increases in the elderly population, there is a paucity of studies examining their surgical outcomes. Objectives: To determine the neurological and functional outcomes of patients over 70 years of age undergoing surgical decompression for subdural hematoma. Materials and Methods: We retrospectively reviewed data on 45 patients above 70 years who underwent craniotomy or burr holes for acute, chronic or mixed subdural hematomas. We analyzed both neurological and functional status before and after surgery. Results: Forty-five patients 70 years of age or older were treated in our department during the study period. There was a significant improvement in the neurological status of patients from admission to follow up as assessed using the Markwalder grading scale (1.98 vs. 1.39; P =0.005, yet no improvement in functional outcome was observed as assessed by Glasgow Outcome Score. Forty-one patients were admitted from home, however only 20 patients (44% were discharged home, 16 (36% discharged to nursing home or rehab, 6 (13% to hospice and 3 (7% died in the postoperative period. Neurological function improved in patients who were older, had a worse pre-operative neurological status, were on anticoagulation and had chronic or mixed acute and chronic hematoma. However, no improvement in functional status was observed. Conclusion: Surgical management of SDH in patients over 70 years of age provides significant improvement in neurological status, but does not change functional status.

  4. Chronic Subdural Hematoma Associated with Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection in Cameroon

    Directory of Open Access Journals (Sweden)

    Clovis Nkoke

    2017-01-01

    Full Text Available Hematological abnormalities including thrombocytopenia are common in patients living with HIV infection. Patients with HIV infection related thrombocytopenia present generally with only minor bleeding problems. But cases of subdural hematoma are very rare. A 61-year-old female with a history of HIV infection of 9 years’ duration presented with a 3-month history of generalized headache associated with visual blurring and anterograde amnesia. There was no history of trauma or fever. She was treated empirically for cerebral toxoplasmosis for 6 weeks without any improvement of the symptoms. One week prior to admission, she developed weakness of the left side of the body. Clinical examination revealed left-sided hemiparesis. Computed tomography scan of the brain showed a 25 mm chronic right frontoparietotemporal subdural hematoma compressing the lateral ventricle with midline shift. There was no appreciable cerebral atrophy. A complete blood count showed leucopenia and thrombocytopenia at 92,000 cells/mm3. Her CD4-positive cell count was 48 cells/mm3 despite receiving combination antiretroviral therapy for 9 years. A complete blood count analysis suggestive of thrombocytopenia should raise suspicion of possibilities of noninfectious focal brain lesions like subdural hematoma amongst HIV infected patients presenting with nonspecific neurological symptoms. This will enable prompt diagnosis and allow early appropriate intervention.

  5. Autoinfection as a cause of postpartum subdural empyema due to Mycoplasma hominis.

    Science.gov (United States)

    Hos, N J; Bauer, C; Liebig, T; Plum, G; Seifert, H; Hampl, J

    2015-04-01

    Mycoplasma hominis is a commensal of the genitourinary tract, which is infrequently associated with urogenital infections. Extra-urogenital infections due to M. hominis are rare. Here, we report an unusual case of M. hominis subdural empyema in a woman occurring shortly after delivery. The patient presented with symptoms suggestive of bacterial meningitis. Spinal imaging revealed a subdural empyema that required neurosurgical intervention. Cultures from intraoperatively obtained biopsies identified M. hominis as the causative pathogen. The patient was treated with oral moxifloxacin for 4 weeks resulting in the resolution of the spinal lesion. The subdural empyema was presumably caused by a contaminated epidural blood patch performed with the patient's own blood during an episode of transient M. hominis bacteremia after delivery. The blood patch was indicated for the treatment of cerebrospinal fluid leakage, which had occurred after epidural anesthesia. Our findings highlight the significance of transient M. hominis bacteremia after delivery and implicate that M. hominis should be considered as a causative agent of extra-genitourinary tract infections particularly during the postpartum period or after genitourinary manipulation.

  6. Parietal subdural empyema as complication of acute odontogenic sinusitis: a case report

    Science.gov (United States)

    2014-01-01

    Introduction To date intracranial complication caused by tooth extractions are extremely rare. In particular parietal subdural empyema of odontogenic origin has not been described. A literature review is presented here to emphasize the extreme rarity of this clinical entity. Case presentation An 18-year-old Caucasian man with a history of dental extraction developed dysarthria, lethargy, purulent rhinorrhea, and fever. A computed tomography scan demonstrated extensive sinusitis involving maxillary sinus, anterior ethmoid and frontal sinus on the left side and a subdural fluid collection in the temporal-parietal site on the same side. He underwent vancomycin, metronidazole and meropenem therapy, and subsequently left maxillary antrostomy, and frontal and maxillary sinuses toilette by an open approach. The last clinical control done after 3 months showed a regression of all symptoms. Conclusions The occurrence of subdural empyema is an uncommon but possible sequela of a complicated tooth extraction. A multidisciplinary approach involving otolaryngologist, neurosurgeons, clinical microbiologist, and neuroradiologist is essential. Antibiotic therapy with surgical approach is the gold standard treatment. PMID:25146384

  7. Subdural empyema, retropharyngeal and parapharyngeal space abscess: Unusual complications of chronic otitis media

    Directory of Open Access Journals (Sweden)

    Erdevički Ljiljana

    2012-01-01

    Full Text Available Introduction. Otitic complications arise from expansion of the middle ear infection. Subdural empyema is a rare otitic complication, and both retropharyngeal and parapharyngeal abscesses have been described in just a few cases. Case report. A 30-year-old male was, admitted as an emergency case because of breathing difficulties, secretion from the ear, and fever. Clinical examination had shown a purulent, fetid secretion from the ear, swelling on the roof of epipharynx, left tonsil pushed medialy, immobile epiglottis, reduced breathing space. Computed tomography revealed thick hypodense content filling cavity, mastoid entering the posterior cranial fossa, descending down throw the parapharyngeal space to the mesopharynx. On the roof and posterior wall of the epipharynx hypodense collection was also present. Tracheotomy was conducted, and incision of the parapharyngeal and retropharyngeal abscess and radical tympanomastoidectomy were performed. The patient’s state deteriorated on the tenth postoperative day with hemiparesis and consciousness disorder. Magnetic resonance imaging was done. It showed subdural empyema of the left frontoparietal region and next to the falx, so craniotomy and abscess drainage were conducted. Conclusion. Parapharyngeal, retropharyngeal abscess and subdural empyema are rare otitic complications. Adequate antibiotic therapy and radical surgical treatment make possible an outcome with survival.

  8. Effect of motivation on academic fluency performance in survivors of pediatric medulloblastoma.

    Science.gov (United States)

    Holland, Alice Ann; Hughes, Carroll W; Harder, Lana; Silver, Cheryl; Bowers, Daniel C; Stavinoha, Peter L

    2016-01-01

    It has been proposed previously that extrinsic motivation may enable survivors of childhood medulloblastoma to significantly improve aspects of neurocognitive performance. In healthy populations, enhanced motivation has been shown to promote academic fluency, a domain likely more relevant to the educational outcomes of pediatric medulloblastoma survivors than academic skill development. The present study investigates the effect of enhanced extrinsic motivation on fluent (i.e., accurate and efficient) academic performance in pediatric medulloblastoma survivors. Participants were 36 children, ages 7-18, who had completed treatment for medulloblastoma. Participants completed a neuropsychological battery that included administration of equivalent tasks on Forms A and B of the Woodcock-Johnson III Tests of Achievement. Half were randomly assigned to an incentive condition prior to the administration of Form B. Provision of a performance-based incentive resulted in statistically significant improvement, but not normalization of function, in performance on measures of academic fluency. No demographic, treatment-related, academic, neuropsychological, or self-perception variables predicted response to incentive. Findings suggest that academic performance of survivors may significantly improve under highly motivating conditions. In addition to implications for educational services, this finding raises the novel possibility that decreased motivation represents an inherent neuropsychological deficit in this population and provides a rationale for further investigation of factors affecting individual differences in motivational processes. Further, by examining effort in a context where effort is not inherently suspect, present findings also significantly contribute to the debate regarding the effects of effort and motivation on neuropsychological performance.

  9. Neurocognitive Function and Health-Related Quality of Life in Pediatric Korean Survivors of Medulloblastoma.

    Science.gov (United States)

    Yoo, Hee Jung; Kim, Hyery; Park, Hyeon Jin; Kim, Dong Seok; Ra, Young Shin; Shin, Hee Young

    2016-11-01

    The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ) score was 86.78, which was within 1 standard deviation of the average score of 100. Processing speed, attention, and executive function showed mild to moderate deficits. Intelligence, memory, executive function, visuospatial function, and simple motor function were significantly lower in the patients diagnosed before 8 years of age compared with those diagnosed after 8. The cognitive deficits in the patients diagnosed at younger ages might be related to earlier exposure to craniospinal irradiation and chemotherapy. The patient and parent proxy evaluations of attention, fine motor function, and quality of life did not differ. We found significant neurocognitive changes in a wide range of neurocognitive functional domains in Korean survivors of childhood medulloblastoma. Long-term follow-up studies of survivors of childhood medulloblastoma beginning at the time of their first diagnosis are required to better understand the deficits exhibited by survivors of childhood medulloblastoma, so that intervention strategies and treatment refinements that reduce the long-term neurocognitive decline can be developed.

  10. FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.

    Science.gov (United States)

    Suryo Rahmanto, Aldwin; Savov, Vasil; Brunner, Andrä; Bolin, Sara; Weishaupt, Holger; Malyukova, Alena; Rosén, Gabriela; Čančer, Matko; Hutter, Sonja; Sundström, Anders; Kawauchi, Daisuke; Jones, David Tw; Spruck, Charles; Taylor, Michael D; Cho, Yoon-Jae; Pfister, Stefan M; Kool, Marcel; Korshunov, Andrey; Swartling, Fredrik J; Sangfelt, Olle

    2016-10-17

    SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCFFBW7α Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. FBW7 is either mutated or downregulated in medulloblastoma, and in cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Transcriptional profiling of medulloblastoma cells expressing a degradation-resistant SOX9 mutant reveals activation of pro-metastatic genes and genes linked to cisplatin resistance. Finally, we show that pharmacological inhibition of PI3K/AKT/mTOR pathway activity destabilizes SOX9 in a GSK3/FBW7-dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  11. Characterization of novel biomarkers in selecting for subtype specific medulloblastoma phenotypes.

    Science.gov (United States)

    Liang, Lisa; Aiken, Christopher; McClelland, Robyn; Morrison, Ludivine Coudière; Tatari, Nazanin; Remke, Marc; Ramaswamy, Vijay; Issaivanan, Magimairajan; Ryken, Timothy; Del Bigio, Marc R; Taylor, Michael D; Werbowetski-Ogilvie, Tamra E

    2015-11-17

    Major research efforts have focused on defining cell surface marker profiles for characterization and selection of brain tumor stem/progenitor cells. Medulloblastoma is the most common primary malignant pediatric brain cancer and consists of 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Given the heterogeneity within and between medulloblastoma variants, surface marker profiles may be subtype-specific. Here, we employed a high throughput flow cytometry screen to identify differentially expressed cell surface markers in self-renewing vs. non-self-renewing SHH medulloblastoma cells. The top 25 markers were reduced to 4, CD271/p75NTR/NGFR, CD106/VCAM1, EGFR and CD171/NCAM-L1, by evaluating transcript levels in SHH tumors relative to samples representing the other variants. However, only CD271/p75NTR/NGFR and CD171/NCAM-L1 maintain differential expression between variants at the protein level. Functional characterization of CD271, a low affinity neurotrophin receptor, in cell lines and primary cultures suggested that CD271 selects for lower self-renewing progenitors or stem cells. Moreover, CD271 levels were negatively correlated with expression of SHH pathway genes. Our study reveals a novel role for CD271 in SHH medulloblastoma and suggests that targeting CD271 pathways could lead to the design of more selective therapies that lessen the broad impact of current treatments on developing nervous systems.

  12. Risk factors for the prognosis of pediatric medulloblastoma: a retrospective analysis of 40 cases.

    Science.gov (United States)

    Yu, Jianzhong; Zhao, Rui; Shi, Wei; Li, Hao

    2017-05-01

    In this study, we evaluated the association of molecular subtypes, clinical characteristics and pathological types with the prognosis of patients with medulloblastoma. We analyzed forty patients with medulloblastoma who underwent surgical resection at our center between January 2004 and June 2014. Risk factors associated with survival, disease progression and recurrence were analyzed with a univariate Cox regression analysis, and the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. Factors associated with overall survival included M stage (p=0.014), calcification (p=0.012), postoperative treatment, postoperative Karnofsky Performance Scale (KPS) score (p=0.015), and molecular subtype (p=0.005 for WNT and p=0.008 for SHH). Number of symptoms (p=0.029), M stage (p2 and ≥M1 stage without postoperative radiotherapy. The risk of recurrence increased with advanced M stage. Protective factors for recurrence included M0 stage and a combination of chemotherapy and radiotherapy. We identified the risk factors associated with survival, disease progression and recurrence of medulloblastoma patients. This information is helpful for understanding the prognostic factors related to medulloblastoma.

  13. RNA Binding Protein-Mediated Post-Transcriptional Gene Regulation in Medulloblastoma

    Science.gov (United States)

    Bish, Rebecca; Vogel, Christine

    2014-01-01

    Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma. PMID:24608801

  14. A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer

    NARCIS (Netherlands)

    Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H. W.; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A.; Vandertop, W. Peter; Noske, David P.; Kaspers, Gertjan J. L.; Würdinger, Tom; Hulleman, Esther

    2016-01-01

    Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of

  15. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition

    NARCIS (Netherlands)

    Kool, Marcel; Jones, David T. W.; Jäger, Natalie; Northcott, Paul A.; Pugh, Trevor J.; Hovestadt, Volker; Piro, Rosario M.; Esparza, L. Adriana; Markant, Shirley L.; Remke, Marc; Milde, Till; Bourdeaut, Franck; Ryzhova, Marina; Sturm, Dominik; Pfaff, Elke; Stark, Sebastian; Hutter, Sonja; Seker-Cin, Huriye; Johann, Pascal; Bender, Sebastian; Schmidt, Christin; Rausch, Tobias; Shih, David; Reimand, Jüri; Sieber, Laura; Wittmann, Andrea; Linke, Linda; Witt, Hendrik; Weber, Ursula D.; Zapatka, Marc; König, Rainer; Beroukhim, Rameen; Bergthold, Guillaume; van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier; Schmidt, Sabine; Wolf, Stephan; Lawerenz, Chris; Bartholomae, Cynthia C.; von Kalle, Christof; Unterberg, Andreas; Herold-Mende, Christel; Hofer, Silvia; Kulozik, Andreas E.; von Deimling, Andreas; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Hasselblatt, Martin; Crawford, John R.; Grant, Gerald A.; Jabado, Nada; Perry, Arie; Cowdrey, Cynthia; Croul, Sydney; Zadeh, Gelareh; Korbel, Jan O.; Doz, Francois; Delattre, Olivier; Bader, Gary D.; McCabe, Martin G.; Collins, V. Peter; Kieran, Mark W.; Cho, Yoon-Jae; Pomeroy, Scott L.; Witt, Olaf; Brors, Benedikt; Taylor, Michael D.; Schüller, Ulrich; Korshunov, Andrey; Eils, Roland; Wechsler-Reya, Robert J.; Lichter, Peter; Pfister, Stefan M.

    2014-01-01

    Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large

  16. Risk-based optimization of photon and proton radiotherapy for pediatric medulloblastoma

    DEFF Research Database (Denmark)

    Brodin, Nils Patrik

    Medulloblastoma (MB) is one of the most common brain tumors in children and most patients will survive their disease if treated with surgery, radio- and chemotherapy. This has resulted in a growing number of MB survivors who are at risk of developing severe late complications related to the aggre...

  17. microRNA-10b Is Overexpressed and Critical for Cell Survival and Proliferation in Medulloblastoma

    Science.gov (United States)

    Pal, Rekha; Greene, Stephanie

    2015-01-01

    This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNA-array, high expression of miRNA-10b in medulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR). Two medulloblastoma cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10b mimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection of miRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, and markedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis of miRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5) and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanism with Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival. PMID:26394044

  18. microRNA-10b Is Overexpressed and Critical for Cell Survival and Proliferation in Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Rekha Pal

    Full Text Available This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNA-array, high expression of miRNA-10b in medulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR. Two medulloblastoma cell lines (DAOY and UW228 were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10b mimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection of miRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, and markedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis of miRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5 and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanism with Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival.

  19. The level of circulating endothelial progenitor cells may be associated with the occurrence and recurrence of chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2013-01-01

    Full Text Available OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct or indirect minor injuries to the head or a poorly repaired vascular injury. Endothelial progenitor cells happen to be one of the key factors involved in hemostasis and vascular repair. This study was designed to observe the levels of endothelial progenitor cells, white blood cells, platelets, and other indicators in the peripheral blood of patients diagnosed with chronic subdural hematoma to determine the possible relationship between the endothelial progenitor cells and the occurrence, development, and outcomes of chronic subdural hematoma. METHOD: We enrolled 30 patients with diagnosed chronic subdural hematoma by computer tomography scanning and operating procedure at Tianjin Medical University General Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of peripheral blood samples from healthy volunteers over the age of 50. Approximately 2 ml of blood was taken from veins of the elbow to test the peripheral blood routine and coagulation function. The content of endothelial progenitor cells in peripheral blood mononuclear cells was determined by flow cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood was significantly lower in preoperational patients with chronic subdural hematomas than in controls. There were no significant differences between the two groups regarding the blood routine and coagulation function. However, the levels of circulating endothelial progenitor cells were significantly different between the recurrent group and the non-recurrent group. CONCLUSIONS: The level of circulating endothelial progenitor cells in chronic subdural hematoma patients was significantly lower than the level in healthy controls. Meanwhile, the level of endothelial progenitor cells in recurrent patients was significantly lower than the level in patients without recurrence. Endothelial progenitor cells may be related to the

  20. Study of hTERT and Histone 3 Mutations in Medulloblastoma.

    Science.gov (United States)

    Viana-Pereira, Marta; Almeida, Gisele Caravina; Stavale, João Norberto; Malheiro, Susana; Clara, Carlos; Lobo, Patrícia; Pimentel, José; Reis, Rui Manuel

    2017-01-01

    Hotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in medulloblastoma. Sixty-nine medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We successfully sequenced hTERT in all 69 medulloblastoma samples and identified a total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT mutations were more frequent in older patients (p < 0.0001), being found only in 5 patients <20 years of age. In addition, hTERT-mutated tumors were more frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent in medulloblastoma and are associated with older patients, prone to recurrence and located in the right cerebellar hemisphere. On the other hand, histone 3 mutations do not seem to be present in medulloblastoma. © 2016 S. Karger AG, Basel.

  1. Survival of children with medulloblastoma in Canada diagnosed between 1990 and 2009 inclusive.

    Science.gov (United States)

    Johnston, Donna L; Keene, Daniel; Kostova, Maria; Lafay-Cousin, Lucie; Fryer, Chris; Scheinemann, Katrin; Carret, Anne-Sophie; Fleming, Adam; Percy, Vanessa; Afzal, Samina; Wilson, Beverly; Bowes, Lynette; Zelcer, Shayna; Mpofu, Chris; Silva, Mariana; Larouche, Valerie; Brossard, Josee; Strother, Douglas; Bouffet, Eric

    2015-09-01

    The treatment of medulloblastoma, the most common malignant brain tumor in children, has evolved over the last few decades. The objectives of this paper were to determine the survival of pediatric medulloblastoma in Canada, to determine if there has been an improvement in the survival rates between the years of 1990 and 2009, inclusive, and to determine prognostic factors for survival. All patients under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009, inclusive, in Canada were included. Data collected included date of diagnosis, age at diagnosis, gender, stage, pathology, treatment, recurrence and current status. From these, survival rates were determined. Data were obtained on 628 eligible patients. The overall 5-year survival rate for the study time period was 69.2 ± 3.3 %. The survival rate increased during the interval of 1996-2000, then remained stable; 1990-1994: 60.2 ± 4.3 %; 1995-1999: 73.2 ± 3.5 %; 2000-2004: 68.8 ± 3.7 %; and 2005-2009: 72.1 ± 4.9 %, p = 0.05. Children over 14 years of age had a significantly better overall survival than those age 5-14 and those under 5 (85.7 ± 5.5 % vs 76.1 ± 2.7 % and 60.8 ± 3 % respectively, p = 0.001). Histologic medulloblastoma subtype and M stage of disease did not result in significant differences in survival. Despite changes in approaches to therapy, we demonstrate a steady survival rate for children with medulloblastoma after 1996. In our analyses, age over 14 years was associated with a higher survival rate.

  2. Resolution of precocious puberty following resection of fourth ventricular medulloblastoma: case report.

    Science.gov (United States)

    Medina, Renata G; Dempsher, David P; Gauvain, Karen M; Geller, Thomas J; Elbabaa, Samer K

    2015-09-01

    Medulloblastoma is a malignant embryonal tumor that arises in the cerebellum and invades the fourth ventricle, often resulting in obstructive hydrocephalus. Patients typically present with symptoms related to increased intracranial pressure and cerebellar dysfunction. The authors report a rare case of classic medulloblastoma with central precocious puberty (CPP) as its only presenting symptom. A 7-year-old boy with no prior history of medulloblastoma presented with Tanner Stage IV testicular enlargement and a 4-month history of acne and pubic hair. Laboratory tests of blood samples demonstrated highly elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Admission MRI of the brain revealed a mass in the posterior fossa, which bordered and compressed the fourth ventricle. The patient also exhibited mild lateral and third ventriculomegaly. Surgical options were discussed with the neurosurgical department. A suboccipital craniotomy and C-1 laminectomy were performed. A large mass was seen arising from the inferior surface of the vermis, and lying within the fourth ventricle. Gross-total microsurgical resection of the mass was performed. Histopathological investigation characterized the tumor as classic medulloblastoma. Follow-up laboratory tests of blood samples demonstrated a reduction of LH, FSH, and testosterone back to prepubertal levels. The patient then began radiation and chemotherapy. This report demonstrates that mild obstructive hydrocephalus due to a posterior fossa tumor may present with unexpected symptoms, such as CPP. To the authors' knowledge, precocious puberty has not yet been associated with medulloblastoma, although it has been found with other posterior fossa tumors. Extensive imaging of the CNS for patients presenting with CPP is recommended.

  3. Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma.

    Science.gov (United States)

    Trubicka, J; Szperl, M; Grajkowska, W; Karkucińska-Więckowska, A; Tarasińska, M; Falana, K; Dembowska-Bagińska, B; Łastowska, M

    2016-01-01

    Rearrangements involving the ALK gene were identified in a variety of cancers, including paediatric tumour neuroblastoma where presence of ALK expression is also associated with adverse prognosis. Microarrays data indicate that ALK is expressed in another paediatric tumour - medulloblastoma. Therefore, we investigated if the ALK gene is mutated in medulloblastoma and performed simultaneously the molecular profiling of tumours. Tumours from sixty-four medulloblastoma patients were studied for detection of ALK alterations in exons 23 and 25 using Sanger method. The molecular subtypes of tumours were identified by detection of mutations in the CTNNB1 gene, monosomy 6 and by immunohistochemistry using a panel of representative antibodies. Among three ALK variants detected two resulted in intron variants (rs3738867, rs113866835) and the third one was a novel heterozygous variant c.3595A>T in exon 23 identified in the WNT type of tumour. It resulted in methionine to leucine substitution at codon position 1199 (M1199L) of the kinase domain of ALK protein. Results of analysis using three in silico algorithms confirmed the pathogenicity of this single nucleotide variation. The same gene alteration was detected in both patient and maternal peripheral blood leukocytes indicating an inherited type of the detected variant. Presence of ALK expression in tumour tissue was confirmed by immunohistochemistry. The tumour was diagnosed as classic medulloblastoma, however with visible areas of focal anaplastic features. The patient has been disease free for 6 years since diagnosis. This is the first evidence of an inherited ALK variant in the WNT type of medulloblastoma, what altogether with presence of ALK expression may point towards involvement of the ALK gene in this type of tumours.

  4. Bmi1 Is Required for Hedgehog Pathway-Driven Medulloblastoma Expansion

    Directory of Open Access Journals (Sweden)

    Lowell Evan Michael

    2008-12-01

    Full Text Available Inappropriate Hedgehog (Hh signaling underlies development of a subset of medulloblastomas, and tumors with elevated HH signaling activity express the stem cell self-renewal gene BMI1. To test whether Bmi1 is required for Hh-driven medulloblastoma development, we varied Bmi1 gene dosage in transgenic mice expressing an oncogenic Hh effector, SmoA1, driven by a glial fibrillary acidic protein (GFAP promoter. Whereas 100% of SmoA1; Bmi1+/+ or SmoA1;Bmi1+/- mice examined between postnatal (P days 14 and 26 had typical medulloblastomas (N = 29, tumors were not detected in any of the SmoA1;Bmi1-/- animals examined (N = 6. Instead, small ectopic collections of cells were present in the region of greatest tumor load in SmoA1 animals, suggesting that medulloblastomas were initiated but failed to undergo expansion into frank tumors. Cells within these Bmi1-/- lesions expressed SmoA1 but were largely nonproliferative, in contrast to cells in Bmi1+/+ tumors (6.2% vs 81.9% PCNA-positive, respectively. Ectopic cells were negative for the progenitor marker nestin, strongly GFAP-positive, and highly apoptotic, relative to Bmi1+/+ tumor cells (29.6% vs 6.3% TUNEL-positive. The alterations in proliferation and apoptosis in SmoA1;Bmi1-/- ectopic cells are associated with reduced levels of Cyclin D1 and elevated expression of cyclin-dependent kinase inhibitor p19Arf, two inversely regulated downstream targets of Bmi1. These data provide the first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain, suggest a crucial role for Bmi1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion, and implicate Bmi1 as a key factor required for Hh pathway-driven tumorigenesis.

  5. Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol.

    Science.gov (United States)

    von Bueren, André O; Friedrich, Carsten; von Hoff, Katja; Kwiecien, Robert; Müller, Klaus; Pietsch, Torsten; Warmuth-Metz, Monika; Hau, Peter; Benesch, Martin; Kuehl, Joachim; Kortmann, Rolf D; Rutkowski, Stefan

    2015-11-01

    Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited. Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy. Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10). Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease. Copyright © 2015 Elsevier Ltd. All rights

  6. Medulloblastoma and Brucellosis - Molecular Evidence of Brucella sp in Association with Central Nervous System Cancer

    Directory of Open Access Journals (Sweden)

    Binxue Zhang, Mina Izadjoo, Iren Horkayne-Szakaly, Alan Morrison, Douglas J. Wear

    2011-01-01

    Full Text Available Neurobrucellosis has been reported to cause lesions in a number of different locations in the central nervous system. Histologically or radiologically, these lesions were consistent with an infection. In response to parents who believed their child's brain tumor, histologically typical of medulloblastoma, was in reality neurobrucellosis, formalin-fixed paraffin-embedded tumor tissue from the medulloblastoma was sectioned, DNA extracted, and tested by polymerase chain reaction (PCR. Specific primer/probe sets, designed in our laboratory to target Brucella species, B. melitensis, B. abortus and B. suis, and designated OMP31, B-m, B-a and B-s, respectively, were used in TaqMan real-time PCR to amplify those gene targets in two separate blocks of the child's tumor. Sections from two blocks were positive only for Brucella species. Although the patient grew up in a European country known to harbor brucella in foods, such as unpasturized milk and cheese, the patient was seronegative for B. mellitensis, B. suis, and B. abortus. In an effort to test whether a relationship existed between the presence of brucella and medulloblastoma, 20 medulloblastomas were retrieved from the tissue repository of the AFIP. The above four primer/probe sets were again used to amplify brucella DNA. Five of 20 tumors (25% contained Brucella species DNA by the OMP31 primer/probe set. None of the 20 medulloblastomas had specific sequences for B. mellitensis, B. suis, or B. abortus. Is chronic brucellosis similar to other infectious agents such as helicobacter that is associated with tumor formation?

  7. CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma.

    Science.gov (United States)

    Dahlin, Anna M; Hollegaard, Mads V; Wibom, Carl; Andersson, Ulrika; Hougaard, David M; Deltour, Isabelle; Hjalmars, Ulf; Melin, Beatrice

    2015-10-01

    Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P(combined) medulloblastoma.

  8. JPO2/CDCA7L and LEDGF/p75 Are Novel Mediators of PI3K/AKT Signaling and Aggressive Phenotypes in Medulloblastoma.

    Science.gov (United States)

    Chan, Tiffany Sin Yu; Hawkins, Cynthia; Krieger, Jonathan R; McGlade, C Jane; Huang, Annie

    2016-05-01

    Substantial evidence links Myc-PI3K/AKT signaling to the most aggressive subtype of medulloblastoma and this axis in medulloblastoma therapy. In this study, we advance understanding of how Myc-PI3K/AKT signaling contributes to this malignancy, specifically, in identifying the Myc-interacting protein JPO2 and its partner binding protein LEDGF/p75 as critical modulators of PI3K/AKT signaling and metastasis in medulloblastoma. JPO2 overexpression induced metastatic medulloblastoma in vivo through two synergistic feed-forward regulatory circuits involving LEDGF/p75 and AKT that promote metastatic phenotypes in this setting. Overall, our findings highlight two novel prometastatic loci in medulloblastoma and point to the JPO2:LEDGF/p75 protein complex as a potentially new targetable component of PI3K/AKT signaling in medulloblastoma. Cancer Res; 76(9); 2802-12. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling.

    Science.gov (United States)

    Li, Cong; Li, Hong; Zhang, Peng; Yu, Li-Jun; Huang, Tian-Miao; Song, Xue; Kong, Qing-You; Dong, Jian-Li; Li, Pei-Nan; Liu, Jia

    2016-12-27

    Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 μM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells.

  10. Long-term life expectancy for children with ependymoma and medulloblastoma.

    Science.gov (United States)

    Frandsen, Jonathan E; Wagner, Aaron; Bollo, Robert J; Shrieve, Dennis C; Poppe, Matthew M

    2015-11-01

    There is a paucity of long-term follow-up data for children with intracranial ependymoma (IE) and medulloblastoma (MB). What happens to these children 20, 30, or 40 years after diagnosis? Do they have potential for a normal lifespan? The purpose of this study was to ascertain the long-term survival potential in children with MB or IE who have survived 5 years from diagnosis. A retrospective analysis was conducted using the SEER Program. Children (ages 0-19 years) from 1973 to 2011 with a diagnosis of MB or IE were identified. A cohort was created of potentially cured patients who survived 5 years from diagnosis. Cox proportional hazards models and Kaplan-Meier estimates were utilized to analyze long-term survival. We identified 876 patients with MB and 474 patients with IE who were alive 5 years from diagnosis. Patients with MB had a 30-year overall survival (OS) and cancer-specific survival (CSS) of 70.2% and 80.1%, respectively. Patients with IE had a 30-year OS and CSS of 57.3% and 68.8%, respectively. When comparing MB with IE, MB had improved CSS (P = 0.04) and trended toward increased OS (P = 0.10). A significant number of deaths due to disease occur for several decades after treatment for both IE and MB. Despite this, the potential for long-term survival exists in 5-year survivors of both histologies. If alive at 5 years from diagnosis, patients with MB tend to have a lower risk of death from disease compared to those with IE. © 2015 Wiley Periodicals, Inc.

  11. Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A.

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    Stephanie Jamison

    Full Text Available Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK in response to endoplasmic reticulum (ER stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A. Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2, to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, and that both VEGF-A and VEGFR2 were required for the promoting effects of PERK activation on medulloblastoma cell migration and invasion. Thus, these findings suggest that moderate PERK activation promotes medulloblastoma cell migration and invasion through enhancement of VEGF-A/VEGFR2 signaling.

  12. Pancreatic Endoplasmic Reticulum Kinase Activation Promotes Medulloblastoma Cell Migration and Invasion through Induction of Vascular Endothelial Growth Factor A

    Science.gov (United States)

    Jamison, Stephanie; Lin, Yifeng; Lin, Wensheng

    2015-01-01

    Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK) in response to endoplasmic reticulum (ER) stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A). Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2), to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, and that both VEGF-A and VEGFR2 were required for the promoting effects of PERK activation on medulloblastoma cell migration and invasion. Thus, these findings suggest that moderate PERK activation promotes medulloblastoma cell migration and invasion through enhancement of VEGF-A/VEGFR2 signaling. PMID:25794107

  13. Inhibition of SIRT1 Transcription inResveratrol-differentiated Medulloblastoma Cells

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    Jing-Xin Ma

    2013-05-01

    Full Text Available ABSTRACTBackgrounds: Medulloblastoma(MB is the commonestbrain malignancyin childhood with poor prognosis, because of itsrapid aggressive growth and frequent occurrence. The current chemotherapeutic regimens for medulloblastoma patients involve a combination of lomustine, cisplatin, carboplatin, vincristine or cyclophosphamide, which have distinct short-and long-term side-effects. It is therefore in urgent need to explore safer and more effective adjuvant approach(s.Resveratrol, a polyphenol rich in numerous plants, has multiple biological activities including anticancer effects. Our previous data confirmed that resveratrolinhibited proliferation and induced differentiation and apoptosis of medulloblastoma cells. SIRT1 is a deacetylase of class III HDACs and the supposed molecular effecter of resveratrol. SIRT1 involves in aging prevention and cancer formation in a cell-context specific manner.Nevertheless, the datum concerningthe role(s ofSIRT1 in formation and prognosis of medulloblastomais still missing.Objective:The present study aimed to address the expression patterna of SIRT1 in medulloblastoma tissuesand non-cancerous counterpartsand to explorewhether resveratrol exerts its anti-medulloblastoma effects via regulating SIRT1 expression and bioactivity.Methods:The expression of SIRT1 in medulloblastoma and non-cancerous counterparts was elucidatedby immunohistochemical ataining (IHC.To clarify the function of SIRT1 in medulloblastomas, SIRT1 expression in UW228-3 medulloblastoma cells were suppressed by RNA interference(RNAi. The influence of resveratrol in SIRT1 expressionsin UW228-3 cellswas analyzedby reverse transcription-polymerase chain reaction (RT-PCR,immunocytochemistry (ICCand Western blotting(WB. The catalytic activity of deacetylase SIRT1was examined by measuring the acetylation ofthe main substrate p53.Results: IHC staining revealedthat SIRT1 was expressed in 64.17% of MB tissues,which was higher than that in

  14. Management of chronic subdural haematoma: burr hole drainage, replacement with Hartmann's solution, and closed-system drainage.

    Science.gov (United States)

    Aung; Wong; Mo; Tsang

    1999-12-01

    Although the treatment of chronic subdural haematoma by burr hole drainage has been performed in the past with or without using a closed drainage system, the problem of intracranial air entrapment still persists and can cause a deterioration in the level of consciousness or seizures in the postoperative period. Cerebral infarction may also develop a few days after surgery because of the intracranial hypotension that occurs during the drainage procedure. In an attempt to minimise these complications and to prevent cerebral infarction and its attendant morbidity, we have developed a technique of treating chronic subdural haematoma-namely, performing burr hole drainage, irrigation and replacement of the haematoma with Hartmann's solution, and closed-system drainage of the subdural space with a silicone catheter. The blood pressure is closely monitored and maintained by the infusion of fluids throughout the procedure. An illustrative case using this technique is presented in this paper.

  15. Two cases of subdural hematoma with niveau formation on CT. A study of the cause of niveau formation

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    Shimizu, Satoshi; Fukuda, Atsuhiro; Sato, Masaharu; Kohama, Akitsugu (Kawasaki Medical School, Kurashiki, Okayama (Japan))

    1984-04-01

    The authors report a case of a bilateral chronic subdural hematoma with niveau formation and another rare case of an acute subdural hematoma with niveau formation on plain CT. The different mechanisms of the niveau formation in these cases are speculated about. The first case was a 75-year-old male who showed a drowsy state, urinary incontinence, and muscle weakness of the bilateral lower limbs. No definite history of head trauma could be found. A plain CT scan showed a bilateral-crescent type fluid collection with niveau formation, consisting of a low-density area in the upper part and a high-density area in the lower part. An operation showed bilateral, moderately encapsulated subdural hematomas; they were evacuated. The second case was a 61-year-old male with head trauma due to a fall from a ladder. On admission, neurological examination revealed a decerebrate posture, a deep coma, and anisocoria. A plain CT scan twenty hours after the onset showed a crescent-type fluid collection with niveau formation in the left fronto-parietal region. The operation showed an acute subdural hematoma containing xanthochromic fluid and coagulated blood. No capsule of hematoma could be seen. The incidence of niveau formation in chronic subdural hematomas is not low (5 - 20%); such niveau formation is thought to be caused by rebleeding into the hematoma and the spending of considerable time in the supine position. On the other hand, no case of an acute subdural hematoma with niveau formation has previously been reported. With regard to this mechanism of niveau formation, we speculate that the hematoma is mixed with cerebrospinal fluid from the arachnoidal tear caused by the head trauma; also, a considerable time in the supine position is necessary.

  16. Sport-Related Structural Brain Injury: 3 Cases of Subdural Hemorrhage in American High School Football.

    Science.gov (United States)

    Yengo-Kahn, Aaron M; Gardner, Ryan M; Kuhn, Andrew W; Solomon, Gary S; Bonfield, Christopher M; Zuckerman, Scott L

    2017-10-01

    The risk of sport-related concussion (SRC) has emerged as a major public health concern. In rare instances, sport-related head injuries can be even more severe, such as subdural hemorrhage, epidural hemorrhage, or malignant cerebral edema. Unlike SRCs, sport-related structural brain injury (SRSBI) is rare, may require neurosurgical intervention, and can lead to permanent neurologic deficit or death. Data characterizing SRSBI are limited, and many have recognized the need to better understand these catastrophic brain injuries. The goal of the current series is to describe, in detail, the presentation, management, and outcomes of examples of these rare injuries. During the fall of 2015, three high school football players presented with acute subdural hemorrhages following in-game collisions and were treated at our institution within a span of 2 months. For the 2 athletes who required surgical intervention, a previous SRC was sustained within 4 weeks before the catastrophic event. One year after injury, 2 players have returned to school, though with persistent deficits. One patient remains nonverbal and wheelchair bound. None of the athletes has returned to sports. Acute subdural hemorrhage resultant from an in-game football collision is rare. The temporal proximity of the reported SRSBIs to recent SRCs emphasizes the importance of return-to-play protocols and raises questions regarding the possibility of second impact syndrome. Although epidemiologic conclusions cannot be drawn from this small sample, these cases provide a unique opportunity to demonstrate the presentation, management, and long-term outcomes of SRSBI in American high school football. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Fatal deterioration of delayed acute subdural hematoma after mild traumatic brain injury: two cases with brief review

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    Chen Shiwen

    2014-04-01

    Full Text Available Both delayed posttraumatic intracerebral hemorrhage and epidural hematoma have been well described in the neurosurgical literatures. However, delayed posttraumatic acute subdural hematoma which happens more than a week with a rapid progress after mild traumatic brain injury and causes death of patient is rarely after mild traumatic brain injury: two cases with brief review reported. We show two such cases and briefly review the literature and discuss the probable pathogenesis of their rapid progress. Key words: Hematoma, subdural, acute; Brain injuries; Delayed diagnosis

  18. Intracranial subdural hematoma after spinal anesthesia for cesarean section: Case report and review of literature

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    Uma Srivastava

    2014-01-01

    Full Text Available Subdural hematoma (SDH is a rare but serious complication of spinal anesthesia. We report a case of intracranial SDH in a patient developing 11 days after spinal anesthesia for cesarean section. The patient complained of headache on the 2nd post-operative day that was relieved by analgesics, bed rest and hydration. Later she presented with severe headache, vomiting, dizziness, dysarthria, irritability and somnolence. Diagnosis of the left sided SDH was confirmed radiologically and treated surgically. The patient recovered completely. The report highlights the need of considering the possibility of SDH in patients when postdural puncture headache is prolonged or recurs after a headache free period with neurological symptoms.

  19. MR imaging of shaken baby syndrome manifested as chronic subdural hematoma

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    Lee, Yul; Lee, Kwan Seop; Hwang, Dae Hyun; Lee, In Jae; Kim, Hyun Beom; Lee, Jae Young [Hallym University College of Medicine, Anyang (Korea, Republic of)

    2001-09-01

    Shaken baby syndrome (SBS) is a form of child abuse that can cause significant head injuries, of which subdural hematoma (SDH) is the most common manifestation. We report the MRI findings of chronic SDH in three cases of SBS, involving two-, three- and eight-month-old babies. The SDH signal was mostly low on T1-weighted images and high on T2-weighted images, suggesting chronic SDH. In chronic SDH, a focal high signal on T1-weighted images was also noted, suggesting rebleeding. Contrast-enhanced MRI revealed diffuse dural enhancement.

  20. Bilateral Ossified Chronic Subdural Hematoma Presenting as Diabetes Insipidus-Case Report and Literature Review.

    Science.gov (United States)

    Siddiqui, Saquib A; Singh, Pankaj Kumar; Sawarkar, Dattaraj; Singh, Manmohanjit; Sharma, Bhawani S

    2017-02-01

    Calcified chronic subdural hematomas are an occurrence rarely seen in neurosurgical clinical practice. And when they occur bilaterally, the radiologic image they present is fascinating, as is the clinical presentation, but their management may be challenging. They have been reported to present with a multitude of neurologic deficits but never with diabetes insipidus, which is described here. Due to the rarity of this pathology, the management protocol is not well defined, though there have been quite a few papers on this condition. This review article gathers information published over the years on this rare entity to suggest a treatment protocol. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A case of Cushing ulcer in an 8-month-old patient with medulloblastoma.

    Science.gov (United States)

    Sivakumar, Walavan; Spader, Heather S; Scaife, Eric; Bollo, Robert J

    2016-04-01

    The authors present the first case of a Cushing ulcer in an infant with medulloblastoma who, despite being administered stress ulcer prophylaxis, worsened after corticosteroids were initiated. An 8-month-old boy presented with progressive vomiting, lethargy, and decreased oral intake. Imaging revealed a heterogeneous fourth ventricular mass. Preoperatively, the patient was started on dexamethasone. The patient underwent an uncomplicated external ventricular drain placement and suboccipital craniotomy for resection of the lesion. The results of the pathological analysis were consistent with medulloblastoma. Postoperatively, the patient had melanotic stools, which were reported to be occurring for months prior to presentation. Two proximal duodenal bulb ulcers were found and required definitive surgical repair. The patient recovered from the acute postsurgical course after continued stress ulcer prophylaxis and is currently undergoing chemotherapy.

  2. Hematoma subdural de medula espinhal associada ao uso de anticoagulante oral Hematoma subdural de la médula espinal asociado al uso de anticoagulante oral Spine subdural hematoma: a rare complication associated with vitamin K antagonist (VKA

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    Uri Adrian Prync Flato

    2009-01-01

    Full Text Available O hematoma subdural de medula espinhal (HSDME é uma complicação rara decorrente do uso de antagonistas de vitamina K (AVK e de diagnostico difícil. Este artigo apresenta um caso com complicação ameaçadora à vida: um paciente octogenário portador de fibrilação atrial de início recente em uso de AVK. A história e o exame físico inicialmente se apresentavam normais, associados com a elevação dos valores de coagulograma supraterapêuticos (INR > 10. Após 24 horas da admissão hospitalar, o paciente apresentou tetraparesia progressiva, evidenciando na ressonância nuclear magnética (RNM de medula espinhal um HSDME (Figura 1. Após reversão completa da hipocoagulação e intervenção neurocirúrgica o paciente obteve melhora do quadro neurológico.El hematoma subdural espinal (HSE es una complicación rara proveniente del uso de antagonistas de vitamina K (AVK y de diagnostico difícil. Este artículo presenta un caso con complicación amenazadora para la vida: un paciente octogenario portador de fibrilación auricular de inicio reciente, en uso de AVK. Inicialmente, la historia y el examen físico se presentaban normales, asociados a la elevación de los valores de coagulograma supra terapéuticos (INR > 10. Tras 24 horas del ingreso hospitalario, el paciente presentó tetraparesia progresiva. Al realizarse una resonancia nuclear magnética (RNM de médula espinal, se evidenció un HSE (Figura 1. Tras reversión completa de la hipocoagulación e intervención neuroquirúrgica el paciente obtuvo mejora del cuadro neurológico.Spinal subdural hematoma (SSDH is a rare condition, which is difficult to diagnose, related to Vitamin K Antagonist. This a case report of a life-threatening situation in a octogenarian patient with a history of recent atrial fibrillation that received K-Vitamin Antagonist (KVA therapy. The history and the clinical assessment were normal at the admission, associated with increase in the coagulation parameters

  3. Na,K-ATPase β1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity.

    Science.gov (United States)

    Lee, Seung Joon; Litan, Alisa; Li, Zhiqin; Graves, Bruce; Lindsey, Stephan; Barwe, Sonali P; Langhans, Sigrid A

    2015-08-19

    The Sonic hedgehog (Shh) signaling pathway plays an important role in cerebellar development, and mutations leading to hyperactive Shh signaling have been associated with certain forms of medulloblastoma, a common form of pediatric brain cancer. While the fundamentals of this pathway are known, the molecular targets contributing to Shh-mediated proliferation and transformation are still poorly understood. Na,K-ATPase is a ubiquitous enzyme that maintains intracellular ion homeostasis and functions as a signaling scaffold and a cell adhesion molecule. Changes in Na,K-ATPase function and subunit expression have been reported in several cancers and loss of the β1-subunit has been associated with a poorly differentiated phenotype in carcinoma but its role in medulloblastoma progression is not known. Human medulloblastoma cell lines and primary cultures of cerebellar granule cell precursors (CGP) were used to determine whether Shh regulates Na,K-ATPase expression. Smo/Smo medulloblastoma were used to assess the Na,K-ATPase levels in vivo. Na,K-ATPase β1-subunit was knocked down in DAOY cells to test its role in medulloblastoma cell proliferation and tumorigenicity. Na,K-ATPase β1-subunit levels increased with differentiation in normal CGP cells. Activation of Shh signaling resulted in reduced β1-subunit mRNA and protein levels and was mimicked by overexpression of Gli1and Bmi1, both members of the Shh signaling cascade; overexpression of Bmi1 reduced β1-subunit promoter activity. In human medulloblastoma cells, low β1-subunit levels were associated with increased cell proliferation and in vivo tumorigenesis. Na,K-ATPase β1-subunit is a target of the Shh signaling pathway and loss of β1-subunit expression may contribute to tumor development and progression not only in carcinoma but also in medulloblastoma, a tumor of neuronal origin.

  4. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

    OpenAIRE

    Dang, Mai T.; Suzanne Wehrli; Dang, Chi V.; Tom Curran

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet...

  5. Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype

    OpenAIRE

    Castro-Gamero, Angel Mauricio; Borges, Kleiton Silva; Lira, Regia Caroline; Andrade, Augusto Faria; Fedatto, Paola Fernanda; Cruzeiro, Gustavo Alencastro Veiga; Silva, Ricardo Bonfim; Fontes,Aparecida Maria; Valera, Elvis Terci; Bobola, Michael; Scrideli,Carlos Alberto; Tone,Luiz Gonzaga

    2013-01-01

    Chromosomal heterogeneity is a hallmark of most tumors and it can drive critical events as growth advantages, survival advantages, progression and karyotypic evolution. Medulloblastoma (MB) is the most common malignant central nervous system tumor in children. This work attempted to investigate chromosomal heterogeneity and instability profiles of two MB pediatric cell lines and their relationship with cell phenotype. We performed GTG-banding and cytokinesis-block micronucleus cytome assays, ...

  6. miR-367 promotes proliferation and stem-like traits in medulloblastoma cells.

    Science.gov (United States)

    Kaid, Carolini; Silva, Patrícia B G; Cortez, Beatriz A; Rodini, Carolina O; Semedo-Kuriki, Patricia; Okamoto, Oswaldo K

    2015-09-01

    In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells. Basal expression of primary and mature forms of miR-367 were detected in four human medulloblastoma cell lines and expression of the latter was found to be upregulated upon enforced expression of OCT4A. Transient overexpression of miR-367 significantly enhanced tumor features typically correlated with poor prognosis; namely, cell proliferation, 3-D tumor spheroid cell invasion and the ability to generate neurosphere-like structures enriched in CD133 expressing cells. A concurrent downregulation of the miR-367 cancer-related targets RYR3, ITGAV and RAB23, was also detected in miR-367-overexpressing cells. Overall, these findings support the pro-oncogenic activity of miR-367 in medulloblastoma and reveal a possible mechanism contributing to tumor aggressiveness, which could be further explored to improve patient stratification and treatment of this important type of pediatric brain cancer. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  7. Postoperative craniospinal radiotherapy of medulloblastoma in children and young adults

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    Golubičić Ivana V.

    2003-01-01

    Full Text Available PURPOSE The aim of this study was: 1. to evaluate treatment results of combined therapy (surgery, postoperative craniospinal radiotherapy with or without chemotherapy and 2. to assess factors affecting prognosis (extend of tumor removal, involvement of the brain stem, extent of disease postoperative meningitis, shunt placement, age, sex and time interval from surgery to start of postoperative radiotherapy. PATIENTS AND METHODS During the period 1986-1996, 78 patients with medulloblastoma, aged 1-22 years (median 8.6 years, were treated with combined modality therapy and 72 of them were evaluable for the study end-points. Entry criteria were histologically proven diagnosis, age under 22 years, and no history of previous malignant disease. The main characteristics of the group are shown in Table 1. Twenty-nine patients (37.2% have total, 8 (10.3% near total and 41 (52.5% partial removal. Seventy-two of 78 patients were treated with curative intent and received postoperative craniospinal irradiation. Radiotherapy started 13-285 days after surgery (median 36 days. Only 13 patients started radiotherapy after 60 days following surgery. Adjuvant chemotherapy was applied in 63 (80.7% patients. The majority of them (46 73% received chemotherapy with CCNU and Vincristine. The survival rates were calculated with the Kaplan-Meier method and the differences in survival were analyzed using the Wilcoxon test and log-rank test. RESULTS The follow-up period ranged from 1-12 years (median 3 years. Five-year overall survival (OS was 51% and disease-free survival (DFS 47% (Graph 1. During follow-up 32 relapses occurred. Patients having no brain stem infiltration had significantly better survival (p=0.0023 (Graph 2. Patients with positive myelographic findings had significantly poorer survival compared to dose with negative myelographic findings (p=0.0116. Significantly poorer survival was found in patients with meningitis developing in the postoperative period

  8. School Competence and Fluent Academic Performance: Informing Assessment of Educational Outcomes in Survivors of Pediatric Medulloblastoma.

    Science.gov (United States)

    Holland, Alice Ann; Hughes, Carroll W; Stavinoha, Peter L

    2015-01-01

    Academic difficulties are widely acknowledged but not adequately studied in survivors of pediatric medulloblastoma. Although most survivors require special education services and are significantly less likely than healthy peers to finish high school, measured academic skills are typically average. This study sought to identify potential factors associated with academic difficulties in this population and focused on school competence and fluent academic performance. Thirty-six patients (ages 7-18 years old) were recruited through the Departments of Neurosurgery and Neuro-Oncology at Children's Medical Center Dallas and Cook Children's Medical Center in Fort Worth, TX. Participants completed a neuropsychological screening battery including selected Woodcock-Johnson III Tests of Achievement subtests. Parents completed the Child Behavior Checklist. School competence was significantly correlated with measured academic skills and fluency. Basic academic skill development was broadly average, in contrast to significantly worse fluent academic performance. School competence may have utility as a measure estimating levels of educational success in this population. Additionally, academic difficulties experienced by childhood medulloblastoma survivors may be better captured by measuring deficits in fluent academic performance rather than skills. Identification of these potential factors associated with educational outcomes of pediatric medulloblastoma survivors has significant implications for research, clinical assessment, and academic services/interventions.

  9. Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications

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    Ferrari Antonio Fernandes

    2003-01-01

    Full Text Available In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method.This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases.The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

  10. A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors

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    Jerome A. Staal

    2016-10-01

    Full Text Available Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC-amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities.

  11. Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy

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    Gidley Paul W

    2011-06-01

    Full Text Available Abstract Background Hearing loss is common following chemoradiotherapy for children with medulloblastoma. Compared to photons, proton radiotherapy reduces radiation dose to the cochlea for these patients. Here we examine whether this dosimetric advantage leads to a clinical benefit in audiometric outcomes. Methods From 2006-2009, 23 children treated with proton radiotherapy for medulloblastoma were enrolled on a prospective observational study, through which they underwent pre- and 1 year post-radiotherapy pure-tone audiometric testing. Ears with moderate to severe hearing loss prior to therapy were censored, leaving 35 ears in 19 patients available for analysis. Results The predicted mean cochlear radiation dose was 30 60Co-Gy Equivalents (range 19-43, and the mean cumulative cisplatin dose was 303 mg/m2 (range 298-330. Hearing sensitivity significantly declined following radiotherapy across all frequencies analyzed (P Conclusions Rates of high-grade early post-radiation ototoxicity following proton radiotherapy for pediatric medulloblastoma are low. Preservation of hearing in the audible speech range, as observed here, may improve both quality of life and cognitive functioning for these patients.

  12. Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

    Science.gov (United States)

    Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang

    2015-09-01

    To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.

  13. A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors.

    Science.gov (United States)

    Staal, Jerome A; Pei, Yanxin; Rood, Brian R

    2016-10-19

    Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC-amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities.

  14. Working memory abilities among children treated for medulloblastoma: parent report and child performance.

    Science.gov (United States)

    Knight, Sarah J; Conklin, Heather M; Palmer, Shawna L; Schreiber, Jane E; Armstrong, Carol L; Wallace, Dana; Bonner, Melanie; Swain, Michelle A; Evankovich, Karen D; Mabbott, Donald J; Boyle, Robyn; Huang, Qinlei; Zhang, Hui; Anderson, Vicki A; Gajjar, Amar

    2014-06-01

    We investigated the 5-year postsurgical developmental trajectory of working memory (WM) in children with medulloblastoma using parent and performance-based measures. This study included 167 patients treated for medulloblastoma. Serial assessments of WM occurred at predetermined time points for 5 years. There was a subtle, statistically significant increase in parental concern about WM, coupled with a statistically significant decrease in age-standardized scores on performance-based measures. However, whole-group mean scores on both parent and performance-based measures remained in the age-expected range. Posterior fossa syndrome was consistently associated with poorer WM. Younger age at treatment and higher treatment intensity were associated with greater negative change in WM performance only. Most children treated for medulloblastoma display WM within the age-appropriate range according to parent report and performance. However, the subtle negative changes over time and identified subgroups at increased risk highlight the need for ongoing monitoring of this population. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47.

    Science.gov (United States)

    Yang, Seung Yeob; Choi, Seung Ah; Lee, Ji Yeoun; Park, Ae-Kyung; Wang, Kyu-Chang; Phi, Ji Hoon; Koh, Eun Jung; Park, Woong-Yang; Park, Sung-Hye; Hwang, Do Won; Jung, Hee Won; Kim, Seung-Ki

    2015-12-22

    The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. During this process, the role of microRNAs (miRs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify the miR involved in leptomeningeal dissemination and to elucidate its biological functional mechanisms. We analyzed the miR expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. Differentially expressed miRs (DEmiRs) were validated in 29 medulloblastoma tissues and three medulloblastoma cell lines. The biological functions of the selected miRs were evaluated using in vitro and in vivo studies. A total of 12 DEmiRs were identified in medulloblastoma with seeding, including miR-192. The reduced expression of miR-192 was confirmed in the tumor seeding group and in the medulloblastoma cells. Overexpression of miR-192 inhibited cellular proliferation by binding DHFR. miR-192 decreased cellular anchoring via the repression of ITGAV, ITGB1, ITGB3, and CD47. Animals in the miR-192-treated group demonstrated a reduction of spinal seeding (P Medulloblastoma with seeding showed specific DEmiRs compared with those without. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability.

  16. MicroRNA 128a Increases Intracellular ROS Level by Targeting Bmi-1 and Inhibits Medulloblastoma Cancer Cell Growth by Promoting Senescence

    Science.gov (United States)

    Venkataraman, Sujatha; Alimova, Irina; Fan, Rong; Harris, Peter; Foreman, Nicholas; Vibhakar, Rajeev

    2010-01-01

    Background MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate cell homeostasis by inhibiting translation or degrading mRNA of target genes, and thereby can act as tumor suppressor genes or oncogenes. The role of microRNAs in medulloblastoma has only recently been addressed. We hypothesized that microRNAs differentially expressed during normal CNS development might be abnormally regulated in medulloblastoma and are functionally important for medulloblastoma cell growth. Methodology and Principal Findings We examined the expression of microRNAs in medulloblastoma and then investigated the functional role of one specific one, miR-128a, in regulating medulloblastoma cell growth. We found that many microRNAs associated with normal neuronal differentiation are significantly down regulated in medulloblastoma. One of these, miR-128a, inhibits growth of medulloblastoma cells by targeting the Bmi-1 oncogene. In addition, miR-128a alters the intracellular redox state of the tumor cells and promotes cellular senescence. Conclusions and Significance Here we report the novel regulation of reactive oxygen species (ROS) by microRNA 128a via the specific inhibition of the Bmi-1 oncogene. We demonstrate that miR-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting Bmi-1. This data has implications for the modulation of redox states in cancer stem cells, which are thought to be resistant to therapy due to their low ROS states. PMID:20574517

  17. Subdural empyema following lumbar facet joint injection: An exceeding rare complication.

    Science.gov (United States)

    Fayeye, Oluwafikayo; Silva, Adikarige Haritha Dulanka; Chavda, Swarupsinh; Furtado, Navin Raoul

    2016-01-01

    Chronic low back pain is extremely common with a life time prevalence estimated at greater than 70%. Facet joint arthrosis is thought to be the causative aetiological substrate in approximately 25% of chronic low back pain cases. Facet joint injection is a routine intervention in the armamentarium for both the diagnostic and therapeutic management of chronic low back pain. In fact, a study by Carrino et al. reported in excess of 94,000 facet joint injection procedures were carried out in the US in 1999. Although generally considered safe, the procedure is not entirely without risk. Complications including bleeding, infection, exacerbation of pain, dural puncture headache, and pneumothorax have been described. We report a rare case of a 47-year-old female patient who developed a left L4/5 facet septic arthrosis with an associated subdural empyema and meningitis following facet joint injection. This case is unique, as to the best of our knowledge no other case of subdural empyema following facet joint injection has been reported in the literature. Furthermore this case serves to highlight the potential serious adverse sequelae of a routine and apparently innocuous intervention. The need for medical practitioners to be alert to and respond rapidly to the infective complications of facet joint injection cannot be understated. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. 3D source localization derived from subdural strip and grid electrodes: a simulation study.

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    Dümpelmann, Matthias; Fell, Jürgen; Wellmer, Jörg; Urbach, Horst; Elger, Christian E

    2009-06-01

    Little experience exists in the application of source reconstruction methods to recordings from subdural strip and grid electrodes. This study addressed the question, whether reliable and accurate 3D source localization is possible from the Electrocorticogram (ECoG). The accuracy of source reconstruction was investigated by simulations and a case study. Simulated sources were used to compute potentials at the electrode positions derived from the MRI of a patient with subdural electrodes. Used procedures were the linear estimation (minimum norm) algorithm and the MUSIC (MUltiple SIgnal Classification) scan. Maxima of linear estimation were attracted to adjacent electrodes. Reliable localization with a localization error 15 mm was only achieved for about 35% of the original source positions. Maxima of the MUSIC metric were identical to original positions for simulations without noise. Noise reduced the percentage of reliable solutions down to a 79.0%. Electrode contacts distant to the source had small influence on localization accuracy. The case study supported simulation results. Reliable source reconstruction derived from ECoG can be achieved by the application of the MUSIC algorithm. Linear estimation needs additional compensation mechanisms. MUSIC based 3D localization based on ECoG has the potential improving epilepsy diagnosis and cognitive research.

  19. Acute subdural empyema. With special reference to CT findings and surgical treatment; case report

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    Sasahira, Masahiro; Takagi, Kenichi; Hashimoto, Kazumasa; Inou, Satoshi; Arai, Toshimoto (Dokkyo Univ., School of Medicine, Tochigi (Japan))

    1983-05-01

    The patient, a 19-year-old male, began suffering from severe headache, vomiting, and high fever. Two days later the patient was admitted in a semicomatose state and with left hemiplegia. Nuchal rigidity and choked disc were not noticed. WBC count was 12,500/mm/sup 3/. CT scan disclosed marked swelling of the right cerebral hemisphere with midline shift. Except for a small lucent space in the parafalcial region, no extracerebral collection was noted in either pre- or post-contrast scans. Plain craniograms showed clouding of the left frontal, ethmoidal, and sphenoidal sinuses. Carotid angiography revealed prolongation of the circulation time and stenosis of the supraclinoidal portion of the right carotid artery. Right fronto-parietal decompressive craniectomy was performed. Subdural empyema was found and evacuated. Curettage and drainage of the empyema in the paranasal sinuses were also done. A bone defect 4 mm in diameter was detected on the medial-upper wall of the left frontal sinus. The causative organism was confirmed as ..cap alpha..-Streptococcus. Both systemic and local antibiotics were administered and the patient recovered well and was discharged without any neurological deficit. The authors emphasized that cerebral angiography is necessary for its accurate diagnosis of subdural empyema in its acute stage and that emergency intracranial and rhino-otological operations should be concomitantly performed.

  20. Isolated oculomotor nerve palsy resulting from acute traumatic tentorial subdural hematoma

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    Cui V

    2016-10-01

    Full Text Available Victoria Cui,1 Timur Kouliev2 1Washington University School of Medicine, St Louis, MO, USA; 2Emergency Department, Beijing United Family Hospital, Beijing, China Abstract: Acute subdural hematoma (SDH resulting from head trauma is a potentially life-threatening condition that requires expedient diagnosis and intervention to ensure optimal patient outcomes. Rapidly expanding or large hematomas, elevated intracranial pressure, and associated complications of brain herniation are associated with high mortality rates and poor recovery of neurological function. However, smaller bleeds (clot thickness <10 mm or hematomas occurring in infrequent locations, such as the tentorium cerebelli, may be difficult to recognize and patients may present with unusual or subtle signs and symptoms, including isolated cranial nerve palsies. Knowledge of neuroanatomy supported by modern neuroimaging can greatly aid in recognition and diagnosis of such lesions. In this report, we present a case of isolated oculomotor nerve palsy resulting from compressive tentorial SDH following blunt head trauma, review the literature concerning similar cases, and make recommendations regarding the diagnosis of SDH in patients presenting with isolated cranial nerve palsies. Keywords: head injury, oculomotor, palsy, subdural hematoma, trauma, tentorium, cerebral herniation, intracranial hemorrhage

  1. Subdural hematomas and emergency management in infancy and childhood: a single institution's experience.

    Science.gov (United States)

    Tehli, Ozkan; Kazanci, Burak; Türkoğlu, Erhan; Solmaz, Ilker

    2011-09-01

    We aimed to identify the incidence, clinical features, management, and outcome of subdural hematomas (SHs) in infancy and childhood. Twenty-one children younger than 11 years with SH were analyzed. Clinical features and possible child abuse were considered in each case. Eight children experienced minor injuries due to hitting of solid items on their head. Five of these children also had coagulation disorders. Three of the children suffered from child abuse, only one of the children had head trauma due to car accident. Nine of the patients experienced SH due to fall down. Nine patients have acute SH, 7 had subacute SH, 4 had chronic SH, and 1 had acute and subacute SH together. Clinical presentation varied greatly. Most of them presented with vomiting and seizure. The outcome patterns were different among the patients. Deep coma on admission was associated with an unfavorable outcome. Subdural hematoma is common in infancy and childhood and carries a poor prognosis. Most of the cases are due to head trauma, coagulation disorders, and child abuse. We believe that clinical investigation of such children should be carried out in a multidisciplinary approach with the collaboration of pediatricians, social workers, and neurosurgeons.

  2. Chronic subdural haematoma management: an iatrogenic complication. Case report and literature review

    Science.gov (United States)

    Vladislav, Pavlov; Bernard, George; Chibbaro, Salvatore

    2012-01-01

    The authors report the case of a 45-year-old woman who presented to our institution with 10 days history of confusion and signs of progressive raised intracranial pressure as a result of a minor head injury occurred 4 weeks before. A brain CT-scan showed a large right hemispheric chronic subdural haematoma which was, as routinely, treated by burr-hole craniostomy and closed-drainage. Although the procedure was uneventful, the next day the patient developed a mild left hemiparesis associated to a slight global status worsening. A brain CT scan showed an intracerebral position of the drain with diffuse brain oedema and midline shift. Following drain removal the patient developed a serious neurological deterioration dropping the Glasgow coma scale to 8/15 as the result of an intracerebral and intraventricular haemorrhage along the removed drain trajectory. The clinical features of this iatrogenic complication are reported analysing also globally chronic subdural haematoma management and discussing pertinent literature. PMID:22669031

  3. A case of atypical chronic subdural hematoma: a spontaneous rupture of dural lymphoma nodule.

    Science.gov (United States)

    Barrios, Lucia; Clément, Renaud; Visseaux, Guillaume; Bord, Eric; Le Gall, Francois; Rodat, Olivier

    2014-02-01

    In forensic medicine, a chronic subdural hematoma (SDH) usually results from trauma, sometimes minimal for elderly people. The case reported here is a forensic medical description of an atypical chronic subdural hematoma. A woman aged of 40-year-old died following a coma. The autopsy and histological analyses revealed the hemorrhagic disintegration of a lymphoid nodule, a metastasis from generalized lymphoma. The combination of chronic symptomatic SDH and a tumor of the dura mater have been described, but are very rare. The possibility of trauma, even minimal, has never been excluded in these cases. In fact, the clinical picture of these patients suggested a significant movement of the brain within the cranial cavity due to the physiological decrease in brain volume. In the reported case, this particular process was excluded since the spontaneous hemorrhagic effusion produced by the meningeal lymphoid nodule was the cause of the chronic SDH. This pathophysiological explanation was possible because the entire brain and meninges were removed for histological analysis. Trauma, even minimal trauma, is not always involved in the formation of a chronic SDH. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  4. Selection of Treatment for Large Non-Traumatic Subdural Hematoma Developed during Hemodialysis

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    Chul Hee Lee

    2014-05-01

    Full Text Available A 49-year-old man with end-stage renal disease was admitted to the hospital with a severe headache and vomiting. On neurological examination the Glasgow Coma Scale (GCS score was 15 and his brain CT showed acute subdural hematoma over the right cerebral convexity with approximately 11-mm thickness and 9-mm midline shift. We chose a conservative treatment of scheduled neurological examination, anticonvulsant medication, serial brain CT scanning, and scheduled hemodialysis (three times per week without using heparin. Ten days after admission, he complained of severe headache and a brain CT showed an increased amount of hemorrhage and midline shift. Emergency burr hole trephination and removal of the hematoma were performed, after which symptoms improved. However, nine days after the operation a sudden onset of general tonic-clonic seizure developed and a brain CT demonstrated an increased amount of subdural hematoma. Under the impression of persistent increased intracranial pressure, the patient was transferred to the intensive care unit (ICU in order to control intracranial pressure. Management at the ICU consisted of regular intravenous mannitol infusion assisted with continuous renal replacement therapy. He stayed in the ICU for four days. Twenty days after the operation he was discharged without specific neurological deficits.

  5. Misdiagnosed spontaneous intracranial hypotension complicated by subdural hematoma following lumbar puncture

    Directory of Open Access Journals (Sweden)

    Louhab N

    2014-01-01

    Full Text Available Nissrine Louhab,1 Nawal Adali,1 Mehdi Laghmari,2 Wafae El Hymer,2 Said Ait Ben Ali,2 Najib Kissani11Neurology Department, 2Neurosurgery Department, University Hospital of Mohammed the VIth, Cadi Ayyad University, Marrakech, MoroccoIntroduction: Spontaneous intracranial hypotension is an infrequent cause of secondary headache due to cerebrospinal fluid (CSF hypovolemia.Objective: To describe a case of headache revealing spontaneous intracranial hypotension complicated by subdural hematoma following lumbar puncture.Observation: A 34-year-old man presented with acute postural headache. The first cerebral computed tomography scan was normal. Lumbar puncture showed hyperproteinorachy at 2 g/L with six lymphocytic cells. The headache became very intense. At admission, clinical examination was normal. Ophthalmological examination did not show any abnormalities. Encephalic magnetic resonance imaging (MRI showed bilateral subdural hematoma with tonsillar descent simulating Chiari type I malformation. After surgical drainage and symptomatic treatment, the patient was discharged with no recurrence.Conclusion: Spontaneous intracranial hypotension is associated with simple clinical presentation, orthostatic headache, and characteristic MRI findings. Misdiagnosed, it leads to unnecessary procedures.Keywords: intracranial hypotension, headache, magnetic resonance imaging

  6. Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord

    Science.gov (United States)

    Sharpe, Abigail N.; Jackson, Andrew

    2014-02-01

    Objective. Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. Approach. Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. Main results. Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2-5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. Significance. We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

  7. Dipole source analyses of early median nerve SEP components obtained from subdural grid recordings.

    Science.gov (United States)

    Baumgärtner, Ulf; Vogel, Hagen; Ohara, Shinji; Treede, Rolf-Detlef; Lenz, Fred A

    2010-12-01

    The median nerve N20 and P22 SEP components constitute the initial response of the primary somatosensory cortex to somatosensory stimulation of the upper extremity. Knowledge of the underlying generators is important both for basic understanding of the initial sequence of cortical activation and to identify landmarks for eloquent areas to spare in resection planning of cortex in epilepsy surgery. We now set out to localize the N20 and P22 using subdural grid recording with special emphasis on the question of the origin of P22: Brodmann area 4 versus area 1. Electroencephalographic dipole source analysis of the N20 and P22 responses obtained from subdural grids over the primary somatosensory cortex after median nerve stimulation was performed in four patients undergoing epilepsy surgery. Based on anatomical landmarks, equivalent current dipoles of N20 and P22 were localized posterior to (n = 2) or on the central sulcus (n = 2). In three patients, the P22 dipole was located posterior to the N20 dipole, whereas in one patient, the P22 dipole was located on the same coordinate in anterior-posterior direction. On average, P22 sources were found to be 6.6 mm posterior [and 1 mm more superficial] compared with the N20 sources. These data strongly suggest a postcentral origin of the P22 SEP component in Brodmann area 1 and render a major precentral contribution to the earliest stages of processing from the primary motor cortex less likely.

  8. Evolution and Prospects for Intracranial Pharmacotherapy for Refractory Epilepsies: The Subdural Hybrid Neuroprosthesis

    Directory of Open Access Journals (Sweden)

    Nandor Ludvig

    2010-01-01

    Full Text Available Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling. AED-delivery systems comprise drug releasing polymers and neuroprosthetic devices that can deliver AEDs into the brain via intraparenchymal, ventricular, or transmeningeal routes. One such device is the subdural Hybrid Neuroprosthesis (HNP, designed to deliver AEDs, such as muscimol, into the subdural/subarachnoid space overlaying neocortical epileptogenic zones, with electrophysiological feedback from the treated tissue. The idea of intracranial pharmacotherapy and HNP treatment for epilepsy originated from multiple sources, including the advent of implanted medical devices, safety data for intracranial electrodes and catheters, evidence for the seizure-controlling efficacy of intracerebral AEDs, and further understanding of the pathophysiology of focal epilepsy. Successful introduction of intracranial pharmacotherapy into clinical practice depends on how the intertwined scientific, engineering, clinical, neurosurgical and regulatory challenges will be met to produce an effective and commercially viable device.

  9. Evolution and prospects for intracranial pharmacotherapy for refractory epilepsies: the subdural hybrid neuroprosthesis.

    Science.gov (United States)

    Ludvig, Nandor; Medveczky, Geza; French, Jacqueline A; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben I

    2010-01-01

    Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling. AED-delivery systems comprise drug releasing polymers and neuroprosthetic devices that can deliver AEDs into the brain via intraparenchymal, ventricular, or transmeningeal routes. One such device is the subdural Hybrid Neuroprosthesis (HNP), designed to deliver AEDs, such as muscimol, into the subdural/subarachnoid space overlaying neocortical epileptogenic zones, with electrophysiological feedback from the treated tissue. The idea of intracranial pharmacotherapy and HNP treatment for epilepsy originated from multiple sources, including the advent of implanted medical devices, safety data for intracranial electrodes and catheters, evidence for the seizure-controlling efficacy of intracerebral AEDs, and further understanding of the pathophysiology of focal epilepsy. Successful introduction of intracranial pharmacotherapy into clinical practice depends on how the intertwined scientific, engineering, clinical, neurosurgical and regulatory challenges will be met to produce an effective and commercially viable device.

  10. Challenging the Pathophysiologic Connection between Subdural Hematoma, Retinal Hemorrhage and Shaken Baby Syndrome

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    Gabaeff, Steven C

    2011-05-01

    Full Text Available Child abuse experts use diagnostic findings of subdural hematoma and retinal hemorrhages as near-pathognomonic findings to diagnose shaken baby syndrome. This article reviews the origin of this link and casts serious doubt on the specificity of the pathophysiologic connection. The forces required to cause brain injury were derived from an experiment of high velocity impacts on monkeys, that generated forces far above those which might occur with a shaking mechanism. These forces, if present, would invariably cause neck trauma, which is conspicuously absent in most babies allegedly injured by shaking. Subdural hematoma may also be the result of common birth trauma, complicated by prenatal vitamin D deficiency, which also contributes to the appearance of long bone fractures commonly associated with child abuse. Retinal hemorrhage is a non-specific finding that occurs with many causes of increased intracranial pressure, including infection and hypoxic brain injury. The evidence challenging these connections should prompt emergency physicians and others who care for children to consider a broad differential diagnosis before settling on occult shaking as the de-facto cause. While childhood non-accidental trauma is certainly a serious problem, the wide exposure of this information may have the potential to exonerate some innocent care-givers who have been convicted, or may be accused, of child abuse. [West J Emerg Med. 2011;12(2:144-158.

  11. Acute Interhemispheric Subdural Hematomas: A Report of 3 Cases and Review of the Literature

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    Osama Shukir Muhammed Amin

    2014-02-01

    Full Text Available The development of acute supratentorial interhemispheric subdural hematomas is an uncommon yet a highly distinct event because of their unusual location, unknown natural history, and debated management. The majority develop in patients with head trauma, generalized bleeding tendency, or coagulopathy. We report on 3 patients who developed spontaneous acute inter-hemispheric subdural hematomas. They were 72, 66, and 65 years old, respectively. Two were males and the 3rd was a female. There was no head trauma, bleeding tendency, or coagulopathy. Two of them were hypertensive but none of them was diabetic, epileptic, or alcoholic. Two patients died, on day 1 and 2 respectively, and the 3rd patient was discharged by his next of kin after 3 hours of admission to our Acute and Emergency department. No neurosurgical intervention was carries out and all patients were treated conservatively. The hematoma was fronto-occipital and was located on the left side in 2 patients while in the 3rd patient it was a right-sided parieto-occipital one. Although the initial investigations had pointed out to the spontaneous development of those hematomas in our patients, a further search for an underlying etiology was supposed to be done, but the early death of 2 patients and the premature discharge of the 3rd patient had intersected with this work-up. The rapid deterioration and death of 2 patients might have been prevented if an early evacuation was done.

  12. Medulloblastoma: correlation among findings of conventional magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy

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    Fonte, Mariana Vieira de Melo da; Otaduy, Maria Concepcion Garcia; Lucato, Leandro Tavares; Reed, Umbertina Conti; Leite, Claudia da Costa [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Inst. de Radiologia]. E-mail: mvmfonte@uol.com.br; Costa, Maria Olivia Rodrigues; Amaral, Raquel Portugal Guimaraes [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Dept. de Radiologia; Reed, Umbertina Conti [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Dept. de Neurologia; Rosemberg, Sergio [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Dept. de Patologia

    2008-11-15

    To correlate imaging findings of medulloblastomas at conventional magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy, comparing them with data in the literature. Preoperative magnetic resonance imaging studies of nine pediatric patients with histologically confirmed medulloblastomas (eight desmoplastic medulloblastoma, and one giant cell medulloblastoma) were retrospectively reviewed, considering demographics as well as tumors characteristics such as localization, morphology, signal intensity, contrast-enhancement, dissemination, and diffusion-weighted imaging and spectroscopy findings. In most of cases the tumors were centered in the cerebellar vermis (77.8%), predominantly solid (88.9%), hypointense on T 1-weighted images and intermediate/hyperintense on T 2-FLAIR-weighted images, with heterogeneous enhancement (100%), tumor dissemination/extension (77.8%) and limited water molecule mobility (100%). Proton spectroscopy acquired with STEAM technique (n = 6) demonstrated decreased Na a / Cr ratio (83.3%) and increased Co/Cr (100%) and ml/Cr (66.7%) ratios; and with PRESS technique (n = 7) demonstrated lactate peak (57.1%). Macroscopic magnetic resonance imaging findings in association with biochemical features of medulloblastomas have been useful in the differentiation among the most frequent posterior fossa tumors. (author)

  13. Head injury, diagnostic X-rays, and risk of medulloblastoma and primitive neuroectodermal tumor: a Children's Oncology Group study.

    Science.gov (United States)

    Khan, Saira; Evans, Alison A; Rorke-Adams, Lucy; Orjuela, Manuela A; Shiminski-Maher, Tania; Bunin, Greta R

    2010-07-01

    A comprehensive case-control study was conducted to determine potential risk factors for medulloblastoma/primitive neuroectodermal tumor (PNET), a common brain tumor in children. This analysis evaluated possible associations between previous head injury and ionizing radiation exposure through diagnostic X-rays and medulloblastoma/PNET. Mothers of 318 cases head injury (OR: 0.78, 95% CI: 0.40-1.5) or head X-ray for any reason including head injury with medulloblastoma/PNET. A statistically non-significant excess of cases reported having an X-ray for reason other than head injury (OR 2.3, 95% CI 0.91-5.7). When cases that received an X-ray for a common symptom of medulloblastoma/PNET were considered unexposed this association weakened (OR: 1.3, 95% CI: 0.49-3.7). No dose-response relationship was observed. Head injury and exposure to diagnostic head X-rays were not associated with medulloblastoma/PNET in this study. Future studies should investigate all imaging procedures with ionizing radiation exposure including computed tomography scans and utilize radiation dose estimations.

  14. ALK Expression Is a Novel Marker for the WNT-activated Type of Pediatric Medulloblastoma and an Indicator of Good Prognosis for Patients.

    Science.gov (United States)

    Łastowska, Maria; Trubicka, Joanna; Niemira, Magdalena; Paczkowska-Abdulsalam, Magdalena; Karkucińska-Więckowska, Agnieszka; Kaleta, Magdalena; Drogosiewicz, Monika; Tarasińska, Magdalena; Perek-Polnik, Marta; Krętowski, Adam; Dembowska-Bagińska, Bożenna; Grajkowska, Wiesława; Pronicki, Maciej; Matyja, Ewa

    2017-06-01

    ALK gene rearrangements were identified in a variety of cancers, including neuroblastoma, where the presence of ALK expression is associated with adverse prognosis. ALK mutations have recently been found in the pediatric brain tumor medulloblastoma, and microarray data indicate that ALK is highly expressed in a subset of these tumors. Therefore, we investigated whether ALK expression correlates with transcriptional profiles and clinical features of medulloblastoma. Tumors from 116 medulloblastoma patients were studied at diagnosis for the detection of ALK expression at the RNA level by an application of NanoString technology and at the protein level by immunohistochemistry using antibody ALK clone D5F3. The results indicate that ALK expression, at both the RNA and the protein levels, is strongly associated with the WNT-activated type of tumors and therefore may serve as a useful marker for the detection of this type of medulloblastoma. Importantly, ALK protein expression alone is also an indicator of good prognosis for medulloblastoma patients.

  15. Source reconstruction based on subdural EEG recordings adds to the presurgical evaluation in refractory frontal lobe epilepsy.

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    Ramantani, Georgia; Cosandier-Rimélé, Delphine; Schulze-Bonhage, Andreas; Maillard, Louis; Zentner, Josef; Dümpelmann, Matthias

    2013-03-01

    In presurgical investigations of refractory frontal lobe epilepsy, subdural EEG recordings offer extensive cortical coverage, but may overlook deep sources. Electrical Source Localization (ESL) from subdural recordings could overcome this sampling limitation. This study aims to assess the clinical relevance of this new method in refractory frontal lobe epilepsy associated with focal cortical dysplasia. In 14 consecutive patients, we retrospectively compared: (i) the ESL of interictal spikes to the conventional irritative and seizure onset zones; (ii) the surgical outcome of cases with congruent ESL and resection volume to cases with incongruent ESL and resection volume. Each spike type was averaged to serve as a template for ESL by the MUSIC and sLORETA algorithms. Results were superimposed on the corresponding pre and post-surgical MRI. Both ESL methods were congruent and consistent with conventional electroclinical analysis in all patients. In 7 cases, ESL identified a common deep source for spikes of different 2D localizations. The inclusion of ESL in the resection volume correlated with seizure freedom. ESL from subdural recordings provided clinically relevant results in patients with refractory frontal lobe epilepsy. ESL complements the conventional analysis of subdural recordings. Its potential in improving tailored resections and surgical outcomes should be prospectively assessed. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Evaluation of awake burr hole drainage for chronic subdural hematoma in geriatric patients: a retrospective analysis of 3 years

    Directory of Open Access Journals (Sweden)

    Serdal Albayrak

    2016-03-01

    Conclusion: Surgical interventions under local anesthesia in geriatric patients with chronic subdural hematoma can provide short operation time, early mobilization, early oral intake, avoidance of possible general anesthesia complications. Herewith, this intervention decrease mortality and morbidity in this age group. [Cukurova Med J 2016; 41(1.000: 69-73

  17. Fatal deterioration of delayed acute subdural hematoma after mild traumatic brain injury: two cases with brief review.

    Science.gov (United States)

    Chen, Shiwen; Xu, Chen; Yuan, Lutao; Tian, Hengli; Cao, Heli; Guo, Yan

    2014-04-01

    Both delayed posttraumatic intracerebral hemorrhage and epidural hematoma have been well described in the neurosurgical literatures. However, delayed posttraumatic acute subdural hematoma which happens more than a week with a rapid progress after mild traumatic brain injury and causes death of patient is rarely reported. We show two such cases and briefly review the literature and discuss the probable pathogenesis of their rapid progress.

  18. Tuberculous brain abscess and subdural empyema in an immunocompetent child: Significance of AFB staining in aspirated pus

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    B Vijayakumar

    2012-01-01

    Full Text Available Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically.

  19. A case of acute spinal subdural hematoma with subarachnoid hemorrhage: Rapid spontaneous remission, relapse, and complete resolution

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    Michito Namekawa

    2017-06-01

    In addition to rostrocaudal spreading of bloody components in the subdural space, rupture of the hematoma into the subarachnoid space must have released pressure, compressing the spinal cord. In this case report, we also describe the serial MRI studies and note the limitations of the resolution of spinal MRI in the acute phase.

  20. Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma.

    Science.gov (United States)

    Merchant, Thomas E; Schreiber, Jane E; Wu, Shengjie; Lukose, Renin; Xiong, Xiaoping; Gajjar, Amar

    2014-11-01

    To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm(2)). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation. Copyright © 2014

  1. Antitumour activity of AMG 900 alone or in combination with histone deacetylase inhibitor SaHa on medulloblastoma cell lines.

    Science.gov (United States)

    Geron, Lenisa; Borges, Kleiton Silva; Andrade, Augusto Faria; Suazo, Veridiana Kill; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga

    2015-08-01

    Medulloblastoma (MB) is the most common malignant childhood brain tumour. Aurora kinases are essential for cell division and are primarily active during mitosis. Recently, the combination of aurora kinases inhibitors (iAURK) and histone deacetylase inhibitors (iHDAC) has shown potential antitumour effects and had significant biological effects in preclinical cancer models. In this study, we analysed the effects of the pan-aurora kinases inhibitor AMG 900 alone or in combination with the iHDAC SaHa (Vorinostat) on paediatric MB cell lines (UW402, UW473 and ONS-76). Cell proliferation was measured by XTT assay, apoptosis was determined by flow cytometry and clonogenic capacity was studied. qRT-PCR assays were used to determine the mRNA expression in MB cell lines after treatment. Drug combination analyses were made based on Chou-Talalay method. AMG 900 caused the inhibition of cell proliferation, diminution of clonogenic capacity and increased the apoptosis rate in cell lines (P AMG900-SaHa combination was evidenced on the inhibition of cell proliferation in all cell lines, especially in sequential drug treatment. Moreover, the combination of these drugs reached 100% of the inhibition in colony formation (synergistic effect). The treatment with AMG 900 increased the p21 and GDF15 expression, but did not alter the TP53 in one of the cell lines. These results indicate that AMG 900 may be a promising drug for the adjuvant treatment of MB, mainly when combined with iHDAC.

  2. Antiangiogenic Therapy in the Treatment of Recurrent Medulloblastoma in the Adult: Case Report and Review of the Literature

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    Giuseppe Privitera

    2009-01-01

    Full Text Available Medulloblastoma is a rare tumor in central nervous system, with an even rarer occurrence in adulthood. The management of a recurrent disease is a medical challenge; chemotherapy has been used as the treatment of choice, while reirradiation has been employed in selected cases. We report the case of a 51-year-old man with recurrent medulloblastoma. He was treated with local reirradiation, chemotherapy, and antiangiogenic drug, with the latter giving the longer progression-free interval. The aim of this report is to show that recurrent medulloblastoma in adults can be approached with a multimodality treatment and that antiangiogenic therapy should have a role in the management of this disease.

  3. Continuous decoding of human grasp kinematics using epidural and subdural signals

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    Flint, Robert D.; Rosenow, Joshua M.; Tate, Matthew C.; Slutzky, Marc W.

    2017-02-01

    Objective. Restoring or replacing function in paralyzed individuals will one day be achieved through the use of brain-machine interfaces. Regaining hand function is a major goal for paralyzed patients. Two competing prerequisites for the widespread adoption of any hand neuroprosthesis are accurate control over the fine details of movement, and minimized invasiveness. Here, we explore the interplay between these two goals by comparing our ability to decode hand movements with subdural and epidural field potentials (EFPs). Approach. We measured the accuracy of decoding continuous hand and finger kinematics during naturalistic grasping motions in five human subjects. We recorded subdural surface potentials (electrocorticography; ECoG) as well as with EFPs, with both standard- and high-resolution electrode arrays. Main results. In all five subjects, decoding of continuous kinematics significantly exceeded chance, using either EGoG or EFPs. ECoG decoding accuracy compared favorably with prior investigations of grasp kinematics (mean ± SD grasp aperture variance accounted for was 0.54 ± 0.05 across all subjects, 0.75 ± 0.09 for the best subject). In general, EFP decoding performed comparably to ECoG decoding. The 7-20 Hz and 70-115 Hz spectral bands contained the most information about grasp kinematics, with the 70-115 Hz band containing greater information about more subtle movements. Higher-resolution recording arrays provided clearly superior performance compared to standard-resolution arrays. Significance. To approach the fine motor control achieved by an intact brain-body system, it will be necessary to execute motor intent on a continuous basis with high accuracy. The current results demonstrate that this level of accuracy might be achievable not just with ECoG, but with EFPs as well. Epidural placement of electrodes is less invasive, and therefore may incur less risk of encephalitis or stroke than subdural placement of electrodes. Accurately decoding motor

  4. Correlations between subdural empyema and paraclinical as well as clinical parameters amongst urban malay paediatric patients.

    Science.gov (United States)

    Nayan, Saiful Azli Mat; Abdullah, Mohd Shafie; Naing, Nyi Nyi; Haspani, Mohd Saffari Mohd; Md Ralib, Ahmad Razali

    2008-10-01

    Paediatric subdural empyema is frequently seen in developing Asean countries secondary to rinosinusogenic origins. A cross-sectional analysis on the surgical treatment of intracranial subdural empyema in Hospital Kuala Lumpur (HKL), a major referral center, was done in 2004. A total number of 44 children who fulfilled the inclusion criteria were included into this study. The methods of first surgery, volume of empyema on contrasted CT brain, improvement of neurological status, re-surgery, mortality and morbidity, as well as the demographic data such as age, gender, sex, duration of illness, clinical presentation, probable origin of empyema, cultures and follow-up were studied. Chi-square test was performed to determine the association between surgical methods and the survival of the patients, neurological improvement, clearance of empyema on CT brain, re-surgery and long morbidity among the survivors. If the 20% or more of the cells were having expected frequency less than five, then Fisher's Exact test was applied. The level of significance was set at 0.05. SPSS version 12.0 was used for data entry and data analysis. There were 44 patients who were less than 18 years. Their mean age was 5.90 ± 6.01 years. There were 30 males (68.2%) and 14 females (31.8%) involved in the study. Malays were majority with 28 (63.6%) followed by Indian 8 (18.2%), Chinese 5 (11.4%) and others 3 (6.8%). The variables which were under interest were gender, race, headache, vomiting, seizures, sign of meningism, cranial nerve palsy, thickness site of abscess, first surgical treatment, improvement in neurological deficit, clearance of CT and whether re-surgery was necessary. All variables were found not to be associated with Henk W Mauser Score for PISDE grading. Comparison between this urban study and a rural setting study by the same corresponding author in the same period on subdural empyema was done. Common parameters were compared and it was found out that seizures were more

  5. Subdural porous and notched mini-grid electrodes for wireless intracranial electroencephalographic recordings

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    Salam MT

    2014-12-01

    Full Text Available Muhammad Tariqus Salam,1 Sébastien Gélinas,1 Sébastien Desgent,2 Sandra Duss,2 Félix Bernier Turmel,1,3 Lionel Carmant,2 Mohamad Sawan,1 Dang Khoa Nguyen3 1Polystim Neurotechnologies Laboratory, Polytechnique Montréal, QC, Canada; 2Research Center, Sainte-Justine University Hospital Center (CHU Sainte-Justine, Université de Montréal, QC, Canada; 3Neurology Service, Department of Medicine, Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal (CHUM, QC, Canada Background: Intracranial electroencephalography (EEG studies are widely used in the presurgical evaluation of drug-refractory patients with partial epilepsy. Because chronic implantation of intracranial electrodes carries a risk of infection, hemorrhage, and edema, it is best to limit the number of electrodes used without compromising the ability to localize the epileptogenic zone (EZ. There is always a risk that an intracranial study may fail to identify the EZ because of suboptimal coverage. We present a new subdural electrode design that will allow better sampling of suspected areas of epileptogenicity with lower risk to patients. Method: Impedance of the proposed electrodes was characterized in vitro using electrochemical impedance spectroscopy. The appearance of the novel electrodes on magnetic resonance imaging (MRI was tested by placing the electrodes into a gel solution (0.9% NaCl with 14 g gelatin. In vivo neural recordings were performed in male Sprague Dawley rats. Performance comparisons were made using microelectrode recordings from rat cortex and subdural/depth recordings from epileptic patients. Histological examinations of rat brain after 3-week icEEG intracerebral electroencephalography (icEEG recordings were performed. Results: The in vitro results showed minimum impedances for optimum choice of pure gold materials for electrode contacts and wire. Different attributes of the new electrodes were identified on MRI. The results of in vivo recordings

  6. Use of twist-drill craniostomy with drain in evacuation of chronic subdural hematomas: independent predictors of recurrence.

    Science.gov (United States)

    Escosa Baé, Marcos; Wessling, Heinrich; Salca, Horia Calin; de Las Heras Echeverría, Pedro

    2011-05-01

    Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques [twist-drill craniostomy (TDC), burr-hole craniostomy, craniotomy] range from 5% to 30%. Use of drain has improved recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors of recurrence of TDC with drain. Three hundred twelve consecutive patients with CSDH have been studied in a retrospective study. Operative technique in all patients consisted in TDC with drain. Data recorded included any associated comorbidity. Radiologic measures of the CSDH before and after the procedure were studied. Clinical evaluation included Modified Rankin Scale, Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared: recurrence group and nonrecurrence group. Follow-up was for at least 1 year. Twelve percent experienced recurrence. Preoperative CSDH width, preoperative midline shift, postoperative midline width, postoperative CSDH width, and residual CSDH 1 month later were significantly associated with CSDH recurrence. The logistic regression model for the multivariate analysis revealed that postoperative midline shift and postoperative neurological deficit were significantly associated with CSDH recurrence. The duration of treatment with dexamethasone was found not to be related with recurrence. Mortality before hospital discharge was 1%. Hospital stay was 2.5 days. TDC with drain has similar results in recurrence rates, morbidity, mortality, and outcome as other techniques as burr-hole craniostomy with drain. Preoperative and postoperative hematoma width and midline shift are independent predictors of recurrence. Brain re-expansion and time of drain maintenance are important factors related with recurrence of CSDH. Future CSDH reservoirs must avoid negative pressure and sudden pressure changes inside the whole closed drain system.

  7. Case report: Extreme levels of serum S-100B in a patient with chronic subdural hematoma

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    Malin Elisabet Persson

    2012-12-01

    Full Text Available The protein S-100B is a biomarker increasingly used within neurosurgery and neurointensive care. As a relatively sensitive, yet unspecific, indicator of CNS pathology, potential sources of error must be clearly understood when interpreting serum S-100B levels. This case report studied the course of a 46-year-old gentleman with a chronic subdural haemorrhage, serum S-100B levels of 22 μg/L and a history of malignant melanoma. Both intra- and extra-cranial sources of S-100B are evaluated and imply an unclear contribution of several sources to the total serum concentration. Potential sources of error when interpreting serum concentrations of S-100B are discussed

  8. Subdural Hematoma: An Adverse Event of Electroconvulsive Therapy—Case Report and Literature Review

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    Ranganath R. Kulkarni

    2012-01-01

    Full Text Available Electroconvulsive therapy (ECT is commonly used in the management of medication nonresponsive depressive disorder, with proven efficacy in psychiatric practice since many decades. A rare complication of intracranial bleed following this therapeutic procedure has been reported in sporadic case reports in the English literature. We report a case of such a complication in a 42-year-old male, a known case of nonorganic medication nonresponsive depressive disorder for the last two years who required ECT application. Presenting symptoms included altered mental state, urinary incontinence, and repeated episodes of vomiting; following ECT procedure with magnetic resonance imaging (MRI of the brain suggestive of bilateral acute subdural hematoma. Despite the view that it may be used in neurological conditions without raised intracranial tension, it will be worthwhile to be vigilant during post-ECT recovery for any emergent complications.

  9. No Value of Routine Brain Computed Tomography 6 Weeks after Evacuation of Chronic Subdural Hematoma

    DEFF Research Database (Denmark)

    Pedersen, Christian Bonde; Sundbye, Filippa; Poulsen, Frantz Rom

    2017-01-01

    Background  The aim of this study was to evaluate the value of planned control postoperative brain computed tomography (CT) scan performed 4 to 6 weeks after the evacuation of chronic subdural hematoma. Materials and Methods  This retrospective study examined 202 patients who during a 2-year period...... was retrieved from patient charts. Results  Overall, 27 out of 202 patients had a recurrence of CSDH and re-evacuation of the hematoma was performed. In all patients recurrence of neurological symptoms preceded the planned postoperative control brain CT 4 to 6 weeks after primary surgery. Conclusion  Routinely...... postoperative control brain CT scan 4 to 6 weeks after the evacuation of a CSDH has no clinical value....

  10. A preliminary study of aquaporin 1 immunolocalization in chronic subdural hematoma membranes.

    Science.gov (United States)

    Basaldella, Luca; Perin, Alessandro; Orvieto, Enrico; Marton, Elisabetta; Itskevich, David; Dei Tos, Angelo Paolo; Longatti, Pierluigi

    2010-07-01

    Aquaporin 1 (AQP1) is a molecular water channel expressed in many anatomical locations, particularly in epithelial barriers specialized in water transport. The aim of this study was to investigate AQP1 expression in chronic subdural hematoma (CSDH) membranes. In this preliminary study, 11 patients with CSDH underwent burr hole craniectomy and drainage. Membrane specimens were stained with a monoclonal antibody targeting AQP1 for immunohistochemical analysis. The endothelial cells of the sinusoid capillaries of the outer membranes exhibited an elevated immunoreactivity to AQP1 antibody compared to the staining intensity of specimens from the inner membrane and normal dura. These findings suggest that the outer membrane might be the source of the increased fluid accumulation responsible for chronic hematoma enlargement.

  11. Clinically silent subdural hemorrhage causes bilateral vocal fold paralysis in newborn infant.

    Science.gov (United States)

    Alshammari, Jaber; Monnier, Yan; Monnier, Philippe

    2012-10-01

    Bilateral congenital vocal fold paralysis (BVFP) may result from multiple etiologies or remain idiopathic when no real cause can be identified. If obstructive dyspnea is significant and requires urgent stabilization of the airway, then intubation is performed first and an MRI of the brain is conducted to rule out an Arnold-Chiari malformation that can benefit from a shunt procedure and thus alleviate the need for a tracheostomy. Clinically silent subdural hemorrhage without any birth trauma represents another cause of neonatal BVFP that resolves spontaneously within a month. It is of clinical relevance to recognize this potential cause of BVFP as its short duration may alleviate the need for a tracheostomy. In this article, we present such a case and review the literature to draw the otolaryngologist's attention to this possible etiology. Copyright © 2012. Published by Elsevier Ireland Ltd.

  12. Post-traumatic epidural and subdural hematomas of the spinal cord in MR imaging; Pourazowe nadoponowe i podoponowe krwiaki rdzenia kregowego w obrazie MR

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    Bronarski, J.; Wozniak, E.; Kiwerski, J. [Stoleczne Centrum Rehabilitacji, Konstancin (Poland)]|[Inst. Psychiatrii i Neurologii, Warsaw (Poland)

    1993-12-31

    Diagnostics of epi- and subdural hematomas of the spinal cord is discussed on the basis of 1992 records of Konstancin Rehabilitation Center. 54 patients with symptoms of partial or complete cord injury were submitted to MR imaging. In 4 cases (7.5%) epi- and subdural hematoma was found to contribute to neurological condition of the patient. MRI determines indications for surgical intervention. (author). 6 refs, 6 figs.

  13. Analysis of Epileptic Discharges from Implanted Subdural Electrodes in Patients with Sturge-Weber Syndrome.

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    Yasushi Iimura

    Full Text Available Almost two-thirds of patients with Sturge-Weber syndrome (SWS have epilepsy, and half of them require surgery for it. However, it is well known that scalp electroencephalography (EEG does not demonstrate unequivocal epileptic discharges in patients with SWS. Therefore, we analyzed interictal and ictal discharges from intracranial subdural EEG recordings in patients treated surgically for SWS to elucidate epileptogenicity in this disorder.Five intractable epileptic patients with SWS who were implanted with subdural electrodes for presurgical evaluation were enrolled in this study. We examined the following seizure parameters: seizure onset zone (SOZ, propagation speed of seizure discharges, and seizure duration by visual inspection. Additionally, power spectrogram analysis on some frequency bands at SOZ was performed from 60 s before the visually detected seizure onset using the EEG Complex Demodulation Method (CDM.We obtained 21 seizures from five patients for evaluation, and all seizures initiated from the cortex under the leptomeningeal angioma. Most of the patients presented with motionless staring and respiratory distress as seizure symptoms. The average seizure propagation speed and duration were 3.1 ± 3.6 cm/min and 19.4 ± 33.6 min, respectively. Significant power spectrogram changes at the SOZ were detected at 10-30 Hz from 15 s before seizure onset, and at 30-80 Hz from 5 s before seizure onset.In patients with SWS, seizures initiate from the cortex under the leptomeningeal angioma, and seizure propagation is slow and persists for a longer period. CDM indicated beta to low gamma-ranged seizure discharges starting from shortly before the visually detected seizure onset. Our ECoG findings indicate that ischemia is a principal mechanism underlying ictogenesis and epileptogenesis in SWS.

  14. Effects of Dexamethasone in the Treatment of Recurrent Chronic Subdural Hematoma.

    Science.gov (United States)

    Zhang, Yu; Chen, Shiping; Xiao, Yangchun; Tang, Wenhua

    2017-09-01

    Recurrent chronic subdural hematoma (CSDH) is not rare. Some studies have demonstrated the role of dexamethasone in the medical management of chronic subdural hematoma. However, no systematic study in the treatment of recurrent CSDH has been published. The aim of our study is to evaluate the efficacy and safety of dexamethasone in patients with recurrent CSDH. We retrospectively reviewed medical records of consecutive patients from July 2010 to September 2014. A total of 27 patients with symptomatic recurrent CSDH were included in the analysis. Follow-up for each patient consisted of computed tomography or magnetic resonance imaging every 28 days from admission to the resolution of hematoma. Data were collected on hematoma volume, complications, and outcome. Among the 27 patients, 3 patients with recurrent CSDH were only treated by burr hole surgery. Of the other 24 patients who primarily underwent dexamethasone treatment, 17 (70.8%) patients were treated successfully with medical treatment, whereas 7 patients required reoperation. Complications were noted in 3 (12.5%) patients (1 hyperglycemia, 1 urinary tract infection, and 1 pneumonia). There was 1 mortality (4.2%) for massive brain infarction. Twenty-one of the 24 patients (87.5%) recovered to their previous functional levels. There was no statistical significance in Fisher text between surgery and dexamethasone regarding success, complication, and functional recovery rate. Patients with recurrent CSDH can be treated successfully and safely with the nonsurgical medical treatment of dexamethasone. By use of this method, reoperation may be avoided. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Functional MRI in medulloblastoma survivors supports prophylactic reading intervention during tumor treatment.

    Science.gov (United States)

    Zou, Ping; Conklin, Heather M; Scoggins, Matthew A; Li, Yimei; Li, Xingyu; Jones, Melissa M; Palmer, Shawna L; Gajjar, Amar; Ogg, Robert J

    2016-03-01

    Development of reading skills is vulnerable to disruption in children treated for brain tumors. Interventions, remedial and prophylactic, are needed to mitigate reading and other learning difficulties faced by survivors. A functional magnetic resonance imaging (fMRI) study was conducted to investigate long-term effects of a prophylactic reading intervention administered during radiation therapy in children treated for medulloblastoma. The fMRI study included 19 reading-intervention (age 11.7 ± 0.6 years) and 21 standard-of-care (age 12.1 ± 0.6 years) medulloblastoma survivors, and 21 typically developing children (age 12.3 ± 0.6 years). The survivors were 2.5 [1.2, 5.4] years after completion of tumor therapies and reading-intervention survivors were 2.9 [1.6, 5.9] years after intervention. Five fMRI tasks (Rapid Automatized Naming, Continuous Performance Test using faces and letters, orthographic and phonological processing of letter pairs, implicit word reading, and story reading) were used to probe reading-related neural activation. Woodcock-Johnson Reading Fluency, Word Attack, and Sound Awareness subtests were used to evaluate reading abilities. At the time of fMRI, Sound Awareness scores were significantly higher in the reading-intervention group than in the standard-of-care group (p = 0.046). Brain activation during the fMRI tasks was detected in left inferior frontal, temporal, ventral occipitotemporal, and subcortical regions, and differed among the groups (p reading-intervention group. Standardized reading scores and patterns of brain activation provide evidence of long-term effects of prophylactic reading intervention in children treated for medulloblastoma.

  16. Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

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    Brown, Aaron P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Barney, Christian L. [Baylor College of Medicine, Houston, Texas (United States); Grosshans, David R.; McAleer, Mary Frances [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Groot, John F. de; Puduvalli, Vinay K. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crawford, Cody N.; Khan, Meena [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Khatua, Soumen [Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Mark R. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-06-01

    Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

  17. Vulnerability of white matter to insult during childhood: evidence from patients treated for medulloblastoma.

    Science.gov (United States)

    Moxon-Emre, Iska; Bouffet, Eric; Taylor, Michael D; Laperriere, Normand; Sharpe, Michael B; Laughlin, Suzanne; Bartels, Ute; Scantlebury, Nadia; Law, Nicole; Malkin, David; Skocic, Jovanka; Richard, Logan; Mabbott, Donald J

    2016-07-01

    OBJECTIVE Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated. METHODS Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the "all-other-treatments" group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15). RESULTS The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p 0.05). CONCLUSIONS Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.

  18. Subdural effusion

    Science.gov (United States)

    ... Long-term antibiotics is usually not needed. Possible Complications Complications of surgery may include: Bleeding Brain damage ... FACP, Attending Neurologist and Assistant Professor of Clinical Neurology, SUNY Stony Brook, School of Medicine, Stony Brook, ...

  19. Phase I trial: safety and feasibility of intracranial electroencephalography using hybrid subdural electrodes containing macro- and microelectrode arrays

    Science.gov (United States)

    Van Gompel, Jamie J.; Stead, S. Matthew; Giannini, Caterina; Meyer, Fredric B.; Marsh, W. Richard; Fountain, Todd; So, Elson; Cohen-Gadol, Aaron; Lee, Kendall H.; Worrell, Gregory A.

    2010-01-01

    Object Cerebral cortex electrophysiology is poorly sampled using standard, low spatial resolution clinical intracranial electrodes. Adding microelectrode arrays to the standard clinical macroelectrode arrays increases the spatial resolution and may ultimately improve the clinical utility of intracranial electroencephalography (iEEG). However, the safety of hybrid electrode systems containing standard clinical macroelectrode and microelectrode arrays is not yet known. The authors report on their preliminary experience in 24 patients who underwent implantation of hybrid electrodes. Methods In this study, 24 consecutive patients underwent long-term iEEG monitoring with implanted hybrid depth and subdural grid and strip electrodes; both clinical macroelectrodes and research microelectrodes were used. The patients included 18 women and 6 men with an average age of 35 ± 12 years (range 21–65). The mean hospital stay was 11 ± 4 days (range 5–20), with mean duration of implantation 7.0 ± 3.2 days (range 3–15). Data from the 198 consecutive craniotomies for standard clinical subdural grid insertion (prior to surgery in the 24 patients described here) were used for comparison to investigate the relative risk of complications. Results Focal seizure identification and subsequent resection was performed in 20 patients. One patient underwent a subsequent operation after neurological deterioration secondary to cerebral swelling and a 5-mm subdural hematoma. There were no infections. The overall complication rate was 4.2% (only 1 patient had a complication), which did not significantly differ from the complication rate previously reported by the authors of 6.6% when standard subdural and depth intracranial electrodes were used. There were no deaths or permanent neurological deficits related to electrode implantation. Conclusions The authors demonstrate the use of hybrid subdural strip and grid electrodes containing high-density microwire arrays and standard clinical

  20. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

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    Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-05-01

    Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

  1. Medulloblastoma arising from an immature teratoma of the posterior fossa. Case report.

    Science.gov (United States)

    Das, Sunit; Muro, Kenji; Goldman, Stewart; Rajaram, Veena; DiPatri, Arthur J

    2007-01-01

    Teratomas, a group of nongerminomatous germ cell tumors, account for 3% of all childhood tumors. These unusual lesions reproduce the cellular and structural phenotypic traits associated with the three classic germ layers in inappropriate places in the body and often retain an embryonal character. These immature cells can differentiate into more malignant neoplasms. An intracranial location for this lesion type is rare. The authors describe the case of a 2-year-old boy with a teratoma of the posterior fossa that had partially differentiated into a medulloblastoma.

  2. Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children.

    Science.gov (United States)

    Kann, Benjamin H; Park, Henry S; Lester-Coll, Nataniel H; Yeboa, Debra N; Benitez, Viviana; Khan, Atif J; Bindra, Ranjit S; Marks, Asher M; Roberts, Kenneth B

    2016-12-01

    Postoperative radiotherapy to the craniospinal axis is standard-of-care for pediatric medulloblastoma but is associated with long-term morbidity, particularly in young children. With the advent of modern adjuvant chemotherapy strategies, postoperative radiotherapy deferral has gained acceptance in children younger than 3 years, although it remains controversial in older children. To analyze recent postoperative radiotherapy national treatment patterns and implications for overall survival in patients with medulloblastoma ages 3 to 8 years. Using the National Cancer Data Base, patients ages 3 to 8 years diagnosed as having histologically confirmed medulloblastoma in 2004 to 2012, without distant metastases, who underwent surgery and adjuvant chemotherapy with or without postoperative radiotherapy at facilities nationwide accredited by the Commission on Cancer were identified. Patients were designated as having "postoperative radiotherapy upfront" if they received radiotherapy within 90 days of surgery or "postoperative radiotherapy deferred" otherwise. Factors associated with postoperative radiotherapy deferral were identified using multivariable logistic regression. Overall survival (OS) was compared using Kaplan-Meier analysis with log-rank tests and multivariable Cox regression. Statistical tests were 2-sided. Postoperative radiotherapy utilization and overall survival. Among 816 patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%) had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year-olds had postoperative radiotherapy deferred (P radiotherapy deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year) and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On survival analysis, with median follow-up of 4.8 years, OS was improved for those receiving postoperative radiotherapy upfront vs postoperative radiotherapy deferred (5-year OS: 82.0% vs 63.4%; P radiotherapy deferral

  3. Subdural and Cerebellar Hematomas Which Developed after Spinal Surgery: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ufuk Utku

    2013-01-01

    Full Text Available Cerebellar hemorrhage following a spinal surgery is extremely rare; however, considering the localization, it can cause major clinical manifestations. While it is considered that these types of bleedings occur secondary to a venous infarct, the pathogenesis is still unclear. A 57-year-old male patient who underwent a laminectomy by exposing T12-L5 and had pedicle screws placed for ankylosing spondylitis developed a CSF leak due to a 2 mm dural tear. A hemorrhage with parallel streaks on the left cerebellar hemisphere was seen in CT scan, and a thin subdural hematoma at right frontotemporal region was seen on cranial MRI, performed after the patient developed intense headache, nausea, vomiting, and stiff neck in the early postoperative period. In this paper, a case of cerebellar and subdural hematomas following a spinal surgery is discussed with its clinical and radiologic findings.

  4. Occult cervical (C1-2) dural tear causing bilateral recurrent subdural hematomas and repaired with cervical epidural blood patch.

    Science.gov (United States)

    Buvanendran, Asokumar; Byrne, Richard W; Kari, Maruti; Kroin, Jeffrey S

    2008-11-01

    The authors report the case of a 56-year-old previously healthy man who presented with a 4-month history of postural headache accompanied by nausea and vomiting. The results of initial imaging studies of the brain were normal. Repeated MR imaging demonstrated bilateral subdural hematomas which were drained and reaccumulated over a period of time. Spinal myelography revealed a cerebrospinal fluid leak at the C1-2 level. A cervical epidural blood patch, with repeated injections of 10 ml autologous blood at the site of the leak, dramatically improved the headache within 24 hours and eliminated the recurrent subdural hematomas. The results of follow-up computed tomography of the brain at 1, 4, 8, and 16 weeks were normal, and at 1-year follow-up the patient was completely free of symptoms and working.

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

    NARCIS (Netherlands)

    E.M. Thompson (Eric M.); T. Hielscher (Thomas); E. Bouffet (Eric); M. Remke (Marc); P. Luu (Phan); S. Gururangan (Sridharan); R.E. McLendon (Roger E.); D.D. Bigner (Darell); E.S. Lipp (Eric S.); S. Perreault (Sebastien); Y.-J. Cho (Yoon-Jae); G. Grant (Gerald); S.-K. Kim (Seung-Ki); J.Y. Lee (Ji Yeoun); A.A.N. Rao (Amulya A. Nageswara); C. Giannini (Caterina); K.K.W. Li (Kay Ka Wai); H.-K. Ng (Ho-Keung); Y. Yao (Yu); T. Kumabe (Toshihiro); T. Tominaga (Teiji); W.A. Grajkowska (Wieslawa); M. Perek-Polnik (Marta); D.C.Y. Low (David C.Y.); W.T. Seow (Wan Tew); K.T.E. Chang (Kenneth T.E.); J. Mora (Jaume); A. Pollack (Aaron); R.L. Hamilton (Ronald L.); S. Leary (Sarah); A.S. Moore (Andrew S.); W.J. Ingram (Wendy J.); A.R. Hallahan (Andrew R.); A. Jouvet (Anne); M. Fèvre-Montange (Michelle); A. Vasiljevic (Alexandre); C. Faure-Conter (Cecile); T. Shofuda (Tomoko); N. Kagawa (Naoki); N. Hashimoto (Naoya); N. Jabado (Nada); A.G. Weil (Alexander G.); T. Gayden (Tenzin); T. Wataya (Takafumi); T. Shalaby (Tarek); M. Grotzer (Michael); K. Zitterbart (Karel); J. Sterba; L. Kren (Leos); T. Hortobágyi (Tibor); A. Klekner (Almos); L. Bognár (László); T. Pócza (Tímea); P. Hauser (Peter); U. Schüller (Ulrich); S. Jung (Shin); W.-Y. Jang (Woo-Youl); P.J. French (Pim); J.M. Kros (Johan); M.L.C. van Veelen-Vincent (Marie-Lise); L. Massimi (Luca); J.R. Leonard (Jeffrey); J.B. Rubin (Joshua); R. Vibhakar (Rajeev); L.B. Chambless (Lola B.); M.K. Cooper (Michael); R.C. Thompson (Reid); R. Faria (Rui); A. Carvalho (Alice); S. Nunes (Sofia); J. Pimentel; X. Fan (Xing); K.M. Muraszko (Karin); E. López-Aguilar (Enrique); D. Lyden (David); L. Garzia (Livia); D.J.H. Shih (David J.); N. Kijima (Noriyuki); C. Schneider (Christian); J. Adamski (Jennifer); P.A. Northcott (Paul A.); M. Kool (Marcel); D. Jones (David); J.A. Chan (Jennifer A.); A. Nikolic (Ana); M.L. Garre (Maria Luisa); E.G. Van Meir (Erwin G.); S. Osuka (Satoru); J.J. Olson (Jeffrey J.); A. Jahangiri (Arman); B.A. Castro (Brandyn A.); N. Gupta (Nalin); W.A. Weiss (William A.); I. Moxon-Emre (Iska); D.J. Mabbott (Donald J.); A. Lassaletta (Alvaro); C.E. Hawkins (Cynthia); U. Tabori (Uri); J. Drake (James); A. Kulkarni (Abhaya); M. Dirks (Maaike); J.T. Rutka (James); A. Korshunov (Andrey); S.M. Pfister (Stefan); R.J. Packer (Roger J.); E.A. Ramaswamy; M.D. Taylor (Michael)

    2016-01-01

    textabstractBackground: 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

  6. Chromatin Accessibility Mapping Identifies Mediators of Basal Transcription and Retinoid-Induced Repression of OTX2 in Medulloblastoma

    Science.gov (United States)

    Zhang, Monica; Song, Lingyun; Lee, Bum-Kyu; Iyer, Vishwanath R.; Furey, Terrence S.; Crawford, Gregory E.; Yan, Hai; He, Yiping

    2014-01-01

    Despite an emerging understanding of the genetic alterations giving rise to various tumors, the mechanisms whereby most oncogenes are overexpressed remain unclear. Here we have utilized an integrated approach of genomewide regulatory element mapping via DNase-seq followed by conventional reporter assays and transcription factor binding site discovery to characterize the transcriptional regulation of the medulloblastoma oncogene Orthodenticle Homeobox 2 (OTX2). Through these studies we have revealed that OTX2 is differentially regulated in medulloblastoma at the level of chromatin accessibility, which is in part mediated by DNA methylation. In cell lines exhibiting chromatin accessibility of OTX2 regulatory regions, we found that autoregulation maintains OTX2 expression. Comparison of medulloblastoma regulatory elements with those of the developing brain reveals that these tumors engage a developmental regulatory program to drive OTX2 transcription. Finally, we have identified a transcriptional regulatory element mediating retinoid-induced OTX2 repression in these tumors. This work characterizes for the first time the mechanisms of OTX2 overexpression in medulloblastoma. Furthermore, this study establishes proof of principle for applying ENCODE datasets towards the characterization of upstream trans-acting factors mediating expression of individual genes. PMID:25198066

  7. Molecular risk stratification of medulloblastoma patients based on immunohistochemical analysis of MYC, LDHB, and CCNB1 expression

    NARCIS (Netherlands)

    de Haas, Talitha; Hasselt, Nancy; Troost, Dirk; Caron, Huib; Popovic, Mara; Zadravec-Zaletel, Lorna; Grajkowska, Wieslawa; Perek, Marta; Osterheld, Maria-Chiara; Ellison, David; Baas, Frank; Versteeg, Rogier; Kool, Marcel

    2008-01-01

    PURPOSE: Medulloblastoma is the most common malignant embryonal brain tumor in children. The current clinical risk stratification to select treatment modalities is not optimal because it does not identify the standard-risk patients with resistant disease or the unknown number of high-risk patients

  8. High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma

    NARCIS (Netherlands)

    Raso, Alessandro; Mascelli, Samantha; Biassoni, Roberto; Nozza, Paolo; Kool, Marcel; Pistorio, Angela; Ugolotti, Elisabetta; Milanaccio, Claudia; Pignatelli, Sara; Ferraro, Manuela; Pavanello, Marco; Ravegnani, Marcello; Cama, Armando; Garrè, Maria Luisa; Capra, Valeria

    2011-01-01

    The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have

  9. Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma

    NARCIS (Netherlands)

    Bunt, Jens; Hasselt, Nancy E.; Zwijnenburg, Danny A.; Koster, Jan; Versteeg, Rogier; Kool, Marcel

    2011-01-01

    Both OTX2 and MYC are important oncogenes in medulloblastoma, the most common malignant brain tumor in childhood. Much is known about MYC binding to promoter regions, but OTX2 binding is hardly investigated. We used ChIP-on-chip data to analyze the binding patterns of both transcription factors in

  10. Post-operative diffusion weighted imaging as a predictor of posterior fossa syndrome permanence in paediatric medulloblastoma.

    Science.gov (United States)

    Chua, Felicia H Z; Thien, Ady; Ng, Lee Ping; Seow, Wan Tew; Low, David C Y; Chang, Kenneth T E; Lian, Derrick W Q; Loh, Eva; Low, Sharon Y Y

    2017-03-01

    Posterior fossa syndrome (PFS) is a serious complication faced by neurosurgeons and their patients, especially in paediatric medulloblastoma patients. The uncertain aetiology of PFS, myriad of cited risk factors and therapeutic challenges make this phenomenon an elusive entity. The primary objective of this study was to identify associative factors related to the development of PFS in medulloblastoma patient post-tumour resection. This is a retrospective study based at a single institution. Patient data and all related information were collected from the hospital records, in accordance to a list of possible risk factors associated with PFS. These included pre-operative tumour volume, hydrocephalus, age, gender, extent of resection, metastasis, ventriculoperitoneal shunt insertion, post-operative meningitis and radiological changes in MRI. Additional variables included molecular and histological subtypes of each patient's medulloblastoma tumour. Statistical analysis was employed to determine evidence of each variable's significance in PFS permanence. A total of 19 patients with appropriately complete data was identified. Initial univariate analysis did not show any statistical significance. However, multivariate analysis for MRI-specific changes reported bilateral DWI restricted diffusion changes involving both right and left sides of the surgical cavity was of statistical significance for PFS permanence. The authors performed a clinical study that evaluated possible risk factors for permanent PFS in paediatric medulloblastoma patients. Analysis of collated results found that post-operative DWI restriction in bilateral regions within the surgical cavity demonstrated statistical significance as a predictor of PFS permanence-a novel finding in the current literature.

  11. Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma

    NARCIS (Netherlands)

    Bunt, J.; Hasselt, N.E.; Zwijnenburg, D.A.; Koster, J.; Versteeg, R.; Kool, M.

    2011-01-01

    Both OTX2 and MYC are important oncogenes in medulloblastoma, the most common malignant brain tumor in childhood. Much is known about MYC binding to promoter regions, but OTX2 binding is hardly investigated. We used ChIP-on-chip data to analyze the binding patterns of both transcription factors in

  12. Exogenous HGF Bypasses the Effects of ErbB Inhibition on Tumor Cell Viability in Medulloblastoma Cell Lines

    NARCIS (Netherlands)

    Zomerman, Waldrik W; Plasschaert, Sabine L. A.; Diks, Sander H.; Lourens, Harm-Jan; Meeuwsen-de Boer, Tiny; Hoving, Eelco W.; den Dunnen, Wilfred F. A.; de Bont, Eveline S. J. M.

    2015-01-01

    Recent clinical trials investigating receptor tyrosine kinase (RTK) inhibitors showed a limited clinical response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed in the brain, such as HGF and EGF, in relation to the effects of hepatocyte

  13. CT and MR imaging findings of subdural dermoid cyst extending into right foramen ovale: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, You Cheol; Park, Cheol Min; Lee, Si Kyeong [Seoul Medical Center, Seoul (Korea, Republic of)

    2006-12-15

    Intracranial dermoid cyst is a rare congenital benign disease, representing less than 0.5% of primary brain tumors. Nevertheless, if ruptured spontaneously or during surgery, it has a poor prognosis due to chemical meningitis. Therefore, it is essential to perform accurate diagnosis and proper treatment. We report an intracranial subdural dermoid cyst that may be misdiagnosed as extracranial or epidural lesion because of extension into the right foramen ovale, and describe the CT and MR imaging findings.

  14. Evaluating the effect of therapeutic stem cells on TRAIL resistant and sensitive medulloblastomas.

    Directory of Open Access Journals (Sweden)

    Irina Nesterenko

    Full Text Available Mesenchymal stem cells (MSC are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines. In TRAIL-resistant MB, we show upregulation of DR4/5 levels when pre-treated with MS-275 and a subsequent sensitization to MSC-S-TRAIL mediated apoptosis. Using intracranially implanted MB and MSC lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that MSC-S-TRAIL has significant anti-tumor effects in mice bearing TRAIL-sensitive and MS-275 pre-treated TRAIL-resistant MBs. To our knowledge, this is the first study that explores the use of human MSC as MB-targeting therapeutic-vehicles in vivo in TRAIL-sensitive and resistant tumors, and has implications for developing effective therapies for patients with medulloblastomas.

  15. Intraoperative Tumoral Bleeding of Hypervascular Medulloblastoma after Ventricular Drainage: A Case Report.

    Science.gov (United States)

    Ryu, Han-Seung; Jung, Tae-Young; Han, Moon-Soo; Kim, Seul-Ki; Lee, Kyung-Hwa

    2017-01-01

    We report a rare case of intraoperative tumoral bleeding of a hypervascular medulloblastoma. A 12-year-old girl presented with dizziness and nausea. Brain magnetic resonance (MR) images revealed an approximately 4.2-cm enhanced mass on the cerebellar vermis associated with mild perilesional edema and increased cerebral blood volume. Angiography showed tumoral staining and developed occipital and circular dural sinuses in the venous phase. A suboccipital craniotomy was performed. To relieve the intracranial pressure, cerebrospinal fluid (CSF) was drained via a lateral ventricular catheter in the occipital horn. During the opening of the dura, the brain swelling had progressed, and brain computed tomography revealed an intratumoral hemorrhage with brainstem compression. The patient was in a stuporous mental state. A reoperation was performed, and the mass was totally removed. The pathologic findings revealed a medulloblastoma with abnormal enlarged arterial vascular structures. Postoperatively, the patient recovered to an alert mental state. She underwent chemotherapy and radiotherapy. There was no recurrence after 1 year. Pre-resectional CSF drainage should not be routinely performed in posterior fossa tumors, especially with increased cerebral blood volume on MR perfusion images. Complete removal should be performed quickly while CSF drainage should be performed slowly. An intratumoral hemorrhage should be considered in posterior fossa tumors when severe brain swelling suddenly develops after CSF drainage. © 2016 S. Karger AG, Basel.

  16. Radiation-induced glioblastoma in a medulloblastoma patient: a case report with molecular features.

    Science.gov (United States)

    Gessi, Marco; Maderna, Emanuela; Guzzetti, Sara; Cefalo, Graziella; Massimino, Maura; Solero, Carlo L; Finocchiaro, Gaetano; Pollo, Bianca

    2008-12-01

    We report a case of glioblastoma (GBM) occurring 8 years after radiation therapy for a medulloblastoma. A 15-year-old boy underwent surgery and radiotherapy for a medulloblastoma and 8 years later he developed a second tumor at the same site. The second lesion showed different histological and molecular features, was diagnosed as a glioblastoma and fulfilled the criteria of radiation-induced neoplasm. Mutational analysis of the p53 gene showed a C to G transition at codon 176 in tumor DNA. LOH was detected at 17p and 19q. The tumor also showed O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and no amplification of EGF receptor. In conclusion, the radiation-induced MGMT hyper-methylation and p53 mutations may have a role in the development of a subgroup of radio-induced glioma (RIG), suggesting that these molecular alterations directly cooperate in the genesis of the post-irradiation GBM. Moreover RIGs seem to be a heterogeneous group of tumors that may resemble either primary or secondary GBM.

  17. Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential.

    Science.gov (United States)

    Fedele, Tommaso; Schönenberger, Claudio; Curio, Gabriel; Serra, Carlo; Krayenbühl, Niklaus; Sarnthein, Johannes

    2017-10-01

    The detectability of high frequency oscillations (HFO, >200Hz) in the intraoperative ECoG is restricted by their low signal-to-noise ratio (SNR). Using the somatosensory evoked HFO, we quantify how HFO detectability can benefit from a custom-made low-noise amplifier (LNA). In 9 patients undergoing tumor surgery in the central region, subdural strip electrodes were placed for intraoperative neurophysiological monitoring. We recorded the somatosensory evoked potential (SEP) simultaneously by custom-made LNA and by a commercial device (CD). We varied the stimulation rate between 1.3 and 12.7Hz to tune the SNR of the N20 component and the evoked HFO and quantified HFO detectability at the single trial level. In three patients we compared Propofol® and Sevoflurane® anesthesia. In the average, amplitude decreased in both in N20 and evoked HFO amplitude with increasing stimulation rate (pnoise amplification improves the detection of the evoked HFO in recordings with subdural electrodes with low impedance. Low-noise EEG might critically improve the detectability of interictal spontaneous HFO in subdural and possibly in scalp recordings. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  18. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  19. Hematoma subdural intracraniano: uma rara complicação após raquianestesia: relato de caso

    Directory of Open Access Journals (Sweden)

    Flora Margarida Barra Bisinotto

    2012-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O hematoma subdural intracraniano é uma complicação rara após raquianestesia. O diagnóstico é muitas vezes difícil porque os sintomas iniciais são os mesmos da cefaleia pós-punção da dura-máter. O objetivo é relatar o caso de um hematoma subdural diag nosticado precocemente, após uma raquianestesia realizada com agulha de calibre fino e punção única. RELATO DO CASO: Paciente de 48 anos, ASA I, submetida a raquianestesia para cirurgia de correção de incontinência urinária. Foi realizada a raquianestesia com agulha 27G Quincke e punção única. A cirurgia foi sem intercorrências, e a paciente recebeu alta hospitalar. Após 48 horas da punção raquidiana, a paciente relatou cefaleia de início súbito, de forte intensidade, acometendo principalmente a região orbitária, mas também a região temporal, com melhora importante no decúbito dorsal e acompanhada de dois episódios de vômitos. Foi solicitada tomografia de crânio que revelou a presença de um hematoma subdural agudo frontotemporoparietal esquerdo. Foi indicado tratamento conservador com analgésicos, dexametasoma e hidantoína. Após 17 dias, apresentou quadro de cefaleia intensa, acompanhada de dormência e paresia do membro superior direito, e distúrbio da fala e comportamento. O hematoma foi drenado cirurgicamente. A paciente evoluiu bem sem sequelas. CONCLUSÕES: A cefaleia é a complicação mais frequente após raquianestesia e é considerada de evolução benigna. Faz com que diagnósticos potencialmente fatais, como o hematoma subdural, não sejam feitos em muitos casos, ou sejam tardios. Este caso descreve uma ocorrência rara, um hematoma subdural agudo após uma raquianestesia com agulha fina em uma paciente sem fatores de risco para sangramento

  20. Risk factors for chronic subdural haematoma formation do not account for the established male bias.

    Science.gov (United States)

    Marshman, Laurence A G; Manickam, Appukutty; Carter, Danielle

    2015-04-01

    The 'subdural space' is an artefact of inner dural border layer disruption: it is not anatomical but always pathological. A male bias has long been accepted for chronic subdural haematomas (CSDH), and increased male frequencies of trauma and/or alcohol abuse are often cited as likely explanations: however, no study has validated this. We investigated to see which risk factors accounted for the male bias with CSDH. Retrospective review of prospectively collected data. A male bias (M:F 97:58) for CSDH was confirmed in n=155 patients. The largest risk factor for CSDH was cerebral atrophy (M:F 94% vs. 91%): whilst a male bias prevailed in mild-moderate cases (M:F 58% vs. 41%), a female bias prevailed for severe atrophy (F:M 50% vs. 36%) (χ(2)=3.88, P=0.14). Risk factors for atrophy also demonstrated a female bias, some approached statistical significance: atrial fibrillation (P=0.05), stroke/TIA (P=0.06) and diabetes mellitus (P=0.07). There was also a trend for older age in females (F:M 72±13 years vs. 68±15 years, P=0.09). The third largest risk factor, after atrophy and trauma (i.e. anti-coagulant and anti-platelet use) was statistically significantly biased towards females (F:M 50% vs. 33%, P=0.04). No risk factor accounted for the established male bias with CSDH. In particular, a history of trauma (head injury or fall [M:F 50% vs. 57%, P=0.37]), and alcohol abuse (M:F 17% vs. 16%, P=0.89) was remarkably similar between genders. No recognised risk factor for CSDH formation accounted for the established male bias: risk factor trends generally favoured females. In particular, and in contrast to popular belief, a male CSDH bias did not relate to increased male frequencies of trauma and/or alcohol abuse. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  1. A systematic review of epileptic seizures in adults with subdural haematomas.

    Science.gov (United States)

    Won, Sae-Yeon; Konczalla, Juergen; Dubinski, Daniel; Cattani, Adriano; Cuca, Colleen; Seifert, Volker; Rosenow, Felix; Strzelczyk, Adam; Freiman, Thomas M

    2017-02-01

    Posttraumatic epileptic seizures (PTS) are a serious complication in patients with subdural haematoma (SDH). However, to date, several studies have shown discordances about SDH-associated seizures in terms of incidence, risk factors and prophylactic antiepileptic treatment. The aim of this study was to analyse the incidence, risk factors of PTS and the role of prophylactic antiepileptic treatment in patients with SDH. A systematic literature review examining PTS in patients with SDH was performed using PubMed gateway, Cochrane Central Register of Controlled Trials, and Excerpta Medica dataBASE between September 1961 and February 2016. Search terms included subdural haematoma, seizure, epilepsy, prophylactic antiepileptic drugs, anticonvulsive medication, and risk factors. Human-based clinical studies focusing on epileptic seizures in patients with SDH. PRISMA statements were used for assessing data quality. Two independent reviewers extracted data from included studies and disagreement was solved by consensus. Twenty-four studies were identified for inclusion into the study. Overall incidence of early PTS (ePTS) and late PTS (lPTS)/2 years was 28% and 43% in acute SDH (aSDH) whereas the incidence of e- and lPTS was lower in chronic SDH (cSDH; 5.3% vs. 10%). Overall risk factors for PTS in patients with aSDH were: 24h postoperative Glasgow Coma Score (GCS) score below 9 (OR 10.5), craniotomy (OR 3.9), preoperative GCS below 8 (OR 3.1). In patients with cSDH the risk factors were alcohol abuse (OR 14.3), change of mental status (OR 7.2), previous stroke (OR 5.3) and density of haematoma in computer tomography (OR 3.8). Age, sex, haematoma size/side and midline shifts were not significant risk factors for PTS in both types of SDH. In prevention of PTS phenytoin and levetiracetam showed similar efficacy (OR 1.3), whereas levetiracetam was associated with significantly lower adverse effects (OR 0.1). Most of the studies were of retrospective nature with a small sample

  2. Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma

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    Brodin, N. Patrik (Radiation Medicine Research Center, Dept. of Radiation Oncology, Rigshospitalet, Univ. of Copenhagen (Denmark); Niels Bohr Inst., Faculty of Sciences, Univ. of Copenhagen (Denmark)), e-mail: brodin.patrik@gmail.com; Munck af Rosenschoeld, Per; Aznar, Marianne C.; Vogelius, Ivan R. (Radiation Medicine Research Center, Dept. of Radiation Oncology, Rigshospitalet, Univ. of Copenhagen (Denmark)); Kiil-Berthelsen, Anne (Radiation Medicine Research Center, Dept. of Radiation Oncology, Rigshospitalet, Univ. of Copenhagen (Denmark); Dept. of Clinical Physiology and Nuclear Medicine, Centre of Diagnostic Investigations, Rigshospitalet, Univ. of Copenhagen (Denmark)); Nilsson, Per; Bjoerk-Eriksson, Thomas (Dept. of Oncology, Skaane Univ. Hospital and Lund Univ., Lund (Sweden)); Lannering, Birgitta (Dept. of Paediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden))

    2011-08-15

    Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WR{sub neutron}). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates

  3. Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating mouse cerebellar neuronal progenitors and medulloblastoma.

    Science.gov (United States)

    Deng, Zhong; Wang, Zhuo; Xiang, Chaomei; Molczan, Aliah; Baubet, Valérie; Conejo-Garcia, Jose; Xu, Xiaowei; Lieberman, Paul M; Dahmane, Nadia

    2012-09-15

    Telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence. Most eukaryotic telomeres can be transcribed to generate a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous nuclear RNA and can be developmentally regulated. However, the precise function and regulation of TERRA in normal and cancer cell development remains poorly understood. Here, we show that TERRA accumulates in highly proliferating normal and cancer cells, and forms large nuclear foci, which are distinct from previously characterized markers of DNA damage or replication stress. Using a mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling, TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates could also be detected in highly proliferating zones of progenitor neurons. SHH could enhance TERRA expression in purified granule progenitor cells in vitro, suggesting that proliferation signals contribute to TERRA expression in responsive tissue. TERRA foci did not colocalize with γH2AX foci, promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue. We also provide evidence that TERRA is elevated in a variety of human cancers. These findings suggest that elevated TERRA levels reflect a novel early form of telomere regulation during replication stress and cancer cell evolution, and the TERRA RNA aggregates may form a novel nuclear body in highly proliferating mammalian cells.

  4. FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Giulia Gentile

    2016-11-01

    Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

  5. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction

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    Korczak, J.F.; Goldstein, A.M. [National Institutes of Health, Bethesda, MD (United States); Kase, R.G. [Westat Inc., Rockville, MD (United States)] [and others

    1997-03-31

    We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.

  6. Syringomyelia following surgery for a spontaneous spinal subdural hematoma in a 13-year-old girl with congenital von Willebrand disease: case report and literature review.

    Science.gov (United States)

    Ben Nsir, A; Boubaker, A; Jemel, H

    2016-04-01

    Spontaneous spinal subdural hematomas are rare. Their occurrence in a child with congenital von Willebrand disease and the complication of their surgery by a large secondary syringomyelia have never been previously reported. A 13-year-old girl with congenital von Willebrand disease presented to our emergency department in January 2011 for sudden onset of severe back pain centered in her thoracic spine rapidly aggravated by signs of acute myelopathy without any precipitating factor. MRI scan revealed a thoracic subdural collection anterior to the spinal cord at the T7-T9 level, hyperintense on T1- and T2-weighted sequences consistent with an acute spinal subdural hemorrhage. Evacuation of the subdural hematoma was realized immediately after hemostasis parameter correction, and post-operative course was uneventful with full functional recovery. One year later, the patient presented once again but with progressive and more severe myelopathy caused by a large syringomyelia extending from the T5 level to the conus medullaris. A syringopleural shunting was performed and the patient was unrolled under an intensive care and rehabilitation program. Her condition remarkably improved and she became able to walk independently within 2 weeks post-operatively. von Willebrand disease should be included as a possible factor of spontaneous spinal subdural hemorrhage. Surgery is advised in emergency and can be associated with remarkable recovery especially in children. Delayed syringomyelia can complicate the post-operative course and can be successfully addressed by syringopleural shunting. Long-term clinical and radiological follow-up is advocated.

  7. Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

    Directory of Open Access Journals (Sweden)

    Quintero Eliana A

    2008-04-01

    Full Text Available Abstract Background This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7 in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13 did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12. The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere and the affectation (or not of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories, Digits span (WISC-R verbal scale and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74 years from surgery in CE group and at 6.47 (SD = 2.77 in CE+ group. Results The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category and moderate to slight deficit in Stroop (word and colour tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables

  8. Double-layer appearance after evacuation of a chronic subdural hematoma.

    Science.gov (United States)

    Sucu, Hasan Kamil; Akar, Ömer

    2014-01-01

    To investigate the reason for and the course of the double-layer appearance in the postoperative computed tomographies (CTs) of chronic subdural hematoma (CSDHs). We reviewed CSDH cases that were operated on during the last 3 years, between January 2008 and December 2010. We checked the preoperative, early postoperative, and late postoperative CTs of these patients. We investigated the relationship between the formation of a double-layer appearance and the prognoses and demographic characteristics of the patients. Our database included 119 cases. A double-layer appearance was found in the postoperative CTs of 34 cases. The mean age of double-layer cases was older (72.5 ± 12.1) than that of the remaining 85 cases (63.1 ± 17.8). We did not find any relationship between the double-layer appearance and the reoperation/recurrence/death rates. The double-layer appearance after evacuation of a CSDH might be caused by enlargement of the subarachnoid space and is not related to the presence of any residual hematoma. This appearance is not considered as a reason for reoperation.

  9. Intracranial subdural hematoma coexisting with improvement in spontaneous intracranial hypotension after an epidural blood patch

    Directory of Open Access Journals (Sweden)

    Cheng-Hsi Chang

    2012-11-01

    Full Text Available A 36-year-old male had spontaneous intracranial hypotension (SIH presenting with refractory headache for 4 months. Multiple epidural blood patches (EBPs yielded relief of symptoms, but the course was complicated, with asymptomatic intracranial subdural hematoma (SDH. Except for SDH, other radiological diagnostic signs of SIH were resolved and the patient’s headaches improved after EBP. Owing to a mass effect and persistent cerebrospinal fluid (CSF leakage, surgical repair of the spinal leakage was performed, but no cranial procedures were carried out. Postoperatively, the SDH completely resolved, but there was still CSF leakage at the level where surgery was performed. The patient has remained free of headache or other events for 3 years. It was reduction rather than elimination of the spinal CSF leak that yielded remission of SIH. In summary, intracranial SDH can be a complication of inadequately treated SIH (i.e. persistent minor CSF leakage. Management of SDH should focus on correction of the underlying SIH rather than craniotomy for hematoma evacuation.

  10. Unilateral Oculomotor Nerve Palsy as an Initial Presentation of Bilateral Chronic Subdural Hematoma: Case Report

    Science.gov (United States)

    Matsuda, Ryosuke; Hironaka, Yasuo; Kawai, Hisashi; Park, Young-Su; Taoka, Toshiaki; Nakase, Hiroyuki

    2013-01-01

    Isolated oculomotor nerve palsy is well known as a symptom of microvascular infarction and intracranial aneurysm, but unilateral oculomotor nerve palsy as an initial manifestation of chronic subdural hematoma (CSDH) is a rare clinical condition. We report a rare case of an 84-year-old woman with bilateral CSDH who presented with unilateral oculomotor nerve palsy as the initial symptom. The patient, who had a medical history of minor head injury 3 weeks prior, presented with left ptosis, diplopia, and vomiting. She had taken an antiplatelet drug for lacunar cerebral infarction. Computed tomography (CT) of the head showed bilateral CSDH with a slight midline shift to the left side. She underwent an urgent evacuation through bilateral frontal burr holes. Magnetic resonance angiography (MRA) after evacuation revealed no intracranial aneurysms, but constructive interference in steady-state (CISS) magnetic resonance imaging (MRI) revealed that the left posterior cerebral artery (PCA) ran much more anteriorly and inferiorly compared with the right PCA and the left oculomotor nerve passed very closely between the left PCA and the left superior cerebellar artery (SCA). There is the possibility that the strong compression to the left uncus, the left PCA, and the left SCA due to the bilateral CSDH resulted in left oculomotor nerve palsy with an initial manifestation without unconsciousness. Unilateral oculomotor nerve palsy as an initial presentation caused by bilateral CSDH without unconsciousness is a rare clinical condition, but this situation is very important as a differential diagnosis of unilateral oculomotor nerve palsy. PMID:24067774

  11. Postoperative anticoagulation in patients with mechanical heart valves following surgical treatment of subdural hematomas.

    Science.gov (United States)

    Amin, Anubhav G; Ng, Julie; Hsu, Wesley; Pradilla, Gustavo; Raza, Shaan; Quinones-Hinojosa, Alfredo; Lim, Michael

    2013-08-01

    Thromboembolic events and anticoagulation-associated bleeding events represent frequent complications following cardiac mechanical valve replacement. Management guidelines regarding the timing for resuming anticoagulation therapy following a surgically treated subdural hematoma (SDH) in patients with mechanical valves remains to be determined. To determine optimal anticoagulation management in patients with mechanical heart valves following treatment of SDH. Outcomes were retrospectively reviewed for 12 patients on anticoagulation therapy for thromboembolic prophylaxis for mechanical cardiac valves who underwent surgical intervention for a SDH at the Johns Hopkins Hospital between 1995 and 2010. The mean age at admission was 71 years. All patients had St. Jude's mechanical heart valves and were receiving anticoagulation therapy. All patients had their anticoagulation reversed with vitamin K and fresh frozen plasma and underwent surgical evacuation. Anticoagulation was withheld for a mean of 14 days upon admission and a mean of 9 days postoperatively. The average length of stay was 19 days. No deaths or thromboembolic events occurred during the hospitalization. Average follow-up time was 50 months, during which two patients had a recurrent SDH. No other associated morbidities occurred during follow-up. Interruptions in anticoagulation therapy for up to 3 weeks pose minimal thromboembolic risk in patients with mechanical heart valves. Close follow-up after discharge is highly recommended, as recurrent hemorrhages can occur several weeks after the resumption of anticoagulation.

  12. Age determination of subdural hematomas with CT and MRI: A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Sieswerda-Hoogendoorn, Tessa, E-mail: t.sieswerda@amc.nl [Section of Forensic Pediatrics, Department of Forensic Medicine, Netherlands Forensic Institute, PO Box 24044, 2490 AA The Hague (Netherlands); Department of Radiology, Academic Medical Center/Emma Children' s Hospital, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Postema, Floor A.M., E-mail: f.a.postema@amc.nl [Faculty of Medicine, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Verbaan, Dagmar, E-mail: d.verbaan@amc.nl [Department of Neurosurgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Majoie, Charles B., E-mail: c.b.majoie@amc.nl [Department of Radiology, Academic Medical Center/Emma Children' s Hospital, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Rijn, Rick R. van, E-mail: r.r.vanrijn@amc.nl [Section of Forensic Pediatrics, Department of Forensic Medicine, Netherlands Forensic Institute, PO Box 24044, 2490 AA The Hague (Netherlands); Department of Radiology, Academic Medical Center/Emma Children' s Hospital, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

    2014-07-15

    Objectives: To systematically review the literature on dating subdural hematomas (SDHs) on CT and MRI scans. Methods: We performed a systematic review in MEDLINE, EMBASE and Cochrane to search for articles that described the appearance of SDHs on CT or MRI in relation to time between trauma and scanning. Two researchers independently screened the articles, assessed methodological quality and performed data extraction. Medians with interquartile ranges were calculated. Differences were tested with a Mann–Whitney U or Kruskal–Wallis H test. Results: We included 22 studies describing 973 SDHs on CT and 4 studies describing 83 SDHs on MRI. Data from 17 studies (413 SDHs) could be pooled. There were significant differences between time intervals for the different densities on CT (p < 0.001). Time interval differed significantly between children and adults for iso- and hypodensity (p = 0.000) and hyperdensity (p = 0.046). Time interval did not differ significantly between abused and non-abused children. On MRI, time intervals for different signal intensities on T1 and T2 did not differ significantly (p = 0.108 and p = 0.194, respectively). Conclusions: Most time intervals of the different appearances of SDHs on CT and MRI are broad and overlapping. Therefore CT or MRI findings cannot be used to accurately date SDHs.

  13. A granulomatous reaction to Avitene mimicking recurrence of a medulloblastoma. Case report.

    Science.gov (United States)

    O'Shaughnessy, Brian A; Schafernak, Kristian T; DiPatri, Arthur J; Goldman, Stewart; Tomita, Tadanori

    2006-01-01

    Microfibrillar collagen hemostat (MCH), also known by its trade name Avitene, is commonly used to control hemorrhage during neurosurgery. Among the documented complications associated with this agent, a granulomatous foreign body reaction is rare, having been described in the central nervous system in only one previous clinical report. In the present study, the authors report the case of a 3-year-old boy who presented with a lesion which appeared to be the recurrence of a tumor 2 months after he had undergone gross-total resection for a medulloblastoma. The patient underwent resection of the presumed recurrent tumor, but histopathological analysis of the specimen revealed a granulomatous foreign body reaction to MCH and no tumor recurrence. In addition to describing the case, the authors review the surgical literature on foreign body reactions to MCH.

  14. Critical Combinations of Radiation Dose and Volume Predict Intelligence Quotient and Academic Achievement Scores After Craniospinal Irradiation in Children With Medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Thomas E., E-mail: thomas.merchant@stjude.org [Division of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Schreiber, Jane E. [Department of Psychology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu, Shengjie [Department of Biostatistcs, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin [Division of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Xiong, Xiaoping [Department of Biostatistcs, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Gajjar, Amar [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2014-11-01

    Purpose: To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. Methods and Materials: Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm{sup 2}). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. Results: A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. Conclusions: The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help

  15. Multicenter pilot study of radio-chemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

    DEFF Research Database (Denmark)

    Dagmar, Dagmar; Proescholdt, Martin; Reinert, Christiane

    2018-01-01

    Background: Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radio-chemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive...... and genetic markers, health-related quality of life (HRQoL) and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after four chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles...... of maintenance chemotherapy. Results: Thirty patients were evaluable. Each 50% percent showed classic and desmoplastic-nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in Non-WNT/Non-SHH. Four cycles...

  16. The use of 5-ALA to assist complete removal of residual non-enhancing part of childhood medulloblastoma

    DEFF Research Database (Denmark)

    Skjøth-Rasmussen, Jane; Bøgeskov, Lars; Sehested, Astrid

    2015-01-01

    PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. Radical surgery in the non-metastatic stage is an important factor with respect to overall survival. In this case, 5-aminolevulinic acid (5-ALA) was used at second-look surgery in order to improve surgical results....... METHODS: The child was pretreated with 3 × 4 mg dexamethasone for 4 days prior to the second surgery. At 5 a.m. on the day of surgery, a freshly prepared solution of 5-ALA (20 mg/kg body weight; Medac, Germany) was given orally. RESULTS: At surgery, through the original opening, the vague red fluorescence...... changed from the high-risk medulloblastoma regimen to the standard-risk regimen. CONCLUSIONS: In this particular difficult case of non-contrast-enhancing tumor, 5-ALA was of vital importance to improve rate of resection and change the aggressiveness needed in postsurgery radiation therapy....

  17. Clinical, pathological, and molecular data on desmoplastic/nodular medulloblastoma: case studies and a review of the literature.

    Science.gov (United States)

    Siegfried, Aurore; Bertozzi, Anne Isabelle; Bourdeaut, Franck; Sevely, Annick; Loukh, Najat; Grison, Camille; Miquel, Catherine; Lafon, Delphine; Sevenet, Nicolas; Pietsch, Torsten; Dufour, Christelle; Delisle, Marie-Bernadette

    2016-01-01

    The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immunoprofile. A 9q deletion was found in 6 cases, a MYCN-MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overallsurvival rates were 72 ± 15% and 85 ± 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence.

  18. Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

    Science.gov (United States)

    Friedman, Gregory K; Moore, Blake P; Nan, Li; Kelly, Virginia M; Etminan, Tina; Langford, Catherine P; Xu, Hui; Han, Xiaosi; Markert, James M; Beierle, Elizabeth A; Gillespie, G Yancey

    2016-02-01

    Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez, Rachel B., E-mail: rbjimenez@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Sethi, Roshan [Harvard Medical School, Boston, Massachusetts (United States); Depauw, Nicolas [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Pulsifer, Margaret B. [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Adams, Judith [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); McBride, Sean M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Ebb, David [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Fullerton, Barbara C.; Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.

  20. Estrogen and soy isoflavonoids decrease sensitivity of medulloblastoma and central nervous system primitive neuroectodermal tumor cells to chemotherapeutic cytotoxicity

    OpenAIRE

    Belcher, Scott M.; Burton, Caleb C.; Cookman, Clifford J.; Kirby, Michelle; Miranda, Gabriel L.; Saeed, Fatima O.; Wray, Kathleen E.

    2017-01-01

    Background Our previous studies demonstrated that growth and migration of medulloblastoma (MB), the most common malignant brain tumor in children, are stimulated by 17?-estradiol. The growth stimulating effects of estrogens are mediated through ER? and insulin-like growth factor 1 signaling to inhibit caspase 3 activity and reduce tumor cell apoptosis. The objective of this study was to determine whether estrogens decreased sensitivity of MB cells to cytotoxic actions of chemotherapeutic drug...

  1. The small molecule, LLL12, inhibits STAT3 phosphorylation and induces apoptosis in medulloblastoma and glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Sarah Ball

    Full Text Available Tumors of the central nervous system represent a major source of cancer-related deaths, with medulloblastoma and glioblastoma being the most common malignant brain tumors in children and adults respectively. While significant advances in treatment have been made, with the 5-year survival rate for medulloblastoma at 70-80%, treating patients under 3 years of age still poses a problem due to the deleterious effects of radiation on the developing brain, and the median survival for patients with glioblastoma is only 15 months. The transcription factor, STAT3, has been found constitutively activated in a wide variety of cancers and in recent years it has become an attractive therapeutic target. We designed a non-peptide small molecule STAT3 inhibitor, LLL12, using structure-based design. LLL12 was able to inhibit STAT3 phosphorylation, decrease cell viability and induce apoptosis in medulloblastoma and glioblastoma cell lines with elevated levels of p-STAT3 (Y705. IC(50 values for LLL12 were found to be between 1.07 µM and 5.98 µM in the five cell lines expressing phosphorylated STAT3. STAT3 target genes were found to be downregulated and a decrease in STAT3 DNA binding was observed following LLL12 treatment, indicating that LLL12 is an effective STAT3 inhibitor. LLL12 was also able to inhibit colony formation, wound healing and decreased IL-6 and LIF secretion. Our results suggest that LLL12 is a potent STAT3 inhibitor and that it may be a potential therapeutic treatment for medulloblastoma and glioblastoma.

  2. Spontaneous Subdural Empyema Following a High-Parasitemia Falciparum Infection in a 58-Year-Old Female From a Malaria-Endemic Region: A Case Report.

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    Pallangyo, Pedro; Lyimo, Frederick; Nicholaus, Paulina; Kain, Ulimbakisya; Janabi, Mohamed

    2016-01-01

    Malaria remains a significant public health problem of the tropical world. Falciparum malaria is most prevalent in the sub-Saharan African region, which harbors about 90% of all malaria cases and fatalities globally. Infection by the falciparum species often manifests with a spectrum of multi-organ complications (eg, cerebral malaria), some of which are life-threatening. Spontaneous subdural empyema is a very rare complication of cerebral malaria that portends a very poor prognosis unless diagnosed and treated promptly. We report a case of spontaneous subdural empyema in a 58-year-old woman from Tanzania who presented with high-grade fever, decreased urine output, and altered sensorium.

  3. Spontaneous Subdural Empyema Following a High-Parasitemia Falciparum Infection in a 58-Year-Old Female From a Malaria-Endemic Region

    Science.gov (United States)

    Pallangyo, Pedro; Lyimo, Frederick; Nicholaus, Paulina; Kain, Ulimbakisya; Janabi, Mohamed

    2016-01-01

    Malaria remains a significant public health problem of the tropical world. Falciparum malaria is most prevalent in the sub-Saharan African region, which harbors about 90% of all malaria cases and fatalities globally. Infection by the falciparum species often manifests with a spectrum of multi-organ complications (eg, cerebral malaria), some of which are life-threatening. Spontaneous subdural empyema is a very rare complication of cerebral malaria that portends a very poor prognosis unless diagnosed and treated promptly. We report a case of spontaneous subdural empyema in a 58-year-old woman from Tanzania who presented with high-grade fever, decreased urine output, and altered sensorium. PMID:27635411

  4. Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord.

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    Dabrowski, Wojciech; Kwiecien, Jacek M; Rola, Radoslaw; Klapec, Michal; Stanisz, Greg J; Kotlinska-Hasiec, Edyta; Oakden, Wendy; Janik, Rafal; Coote, Margaret; Frey, Benicio N; Turski, Waldemar A

    2015-01-01

    Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown. The aim of this study was to assess the effect of the subdural KYNA infusion on the spinal cord in adult rats. A total of 42 healthy adult rats were randomly assigned into six groups and were infused for 7 days with PBS (control) or 0.0002 pmol/min, 0.01 nmol/min, 0.1 nmol/min, 1 nmol/min, and 10 nmol/min of KYNA per 7 days. The effect of KYNA on spinal cord was determined using histological and electron microscopy examination. Myelin oligodendrocyte glycoprotein (MOG) was measured in the blood serum to assess a degree of myelin damage. In all rats continuous long-lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub-pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia. We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role of KYNA in control of physiological

  5. Risks and benefits of invasive epilepsy surgery workup with implanted subdural and depth electrodes.

    Science.gov (United States)

    Wellmer, Jörg; von der Groeben, Ferdinand; Klarmann, Ute; Weber, Christian; Elger, Christian E; Urbach, Horst; Clusmann, Hans; von Lehe, Marec

    2012-08-01

    In patients with pharmacoresistant focal-onset seizures, invasive presurgical workup can identify epilepsy surgery options when noninvasive workup has failed. Yet, the potential benefit must be balanced with procedure-related risks. This study examines risks associated with the implantation of subdural strip and grid, and intracerebral depth electrodes. Benefit of invasive monitoring is measured by seizure outcomes. Diagnostic procedures made possible by electrode implantation are described. Retrospective evaluation of invasive workups in 242 epilepsy surgery candidates and additional 18 patients with primary brain tumors implanted for mapping only. Complications are scaled in five grades of severity. A regression analysis identifies risk factors for complications. Outcome is classified according to Engel's classification. Complications of any type were documented in 23% of patients, and complications requiring surgical revision in 9%. We did not find permanent morbidity or mortality. Major risk factor for complications was the implantation of grids and the implantation of electrode assemblies comprising strip and grid electrodes. Depth electrodes were significantly correlated with a lower risk. Tumors were not correlated with higher complication rates. Chronic invasive monitoring of 3-40 days allowed seizure detection in 99.2% of patients with epilepsy and additional extensive mapping procedures. Patients with epilepsy with follow-up >24 months (n = 165) had an Engel class 1a outcome in 49.7% if epilepsy surgery was performed, but only 6.3% when surgery was rejected. The benefit of chronic invasive workup outweighs its risks, but complexity of implantations should be kept to a minimum. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  6. Seizure Correlates with Prolonged Hospital Stay, Increased Costs, and Increased Mortality in Nontraumatic Subdural Hematoma.

    Science.gov (United States)

    Joseph, Jacob R; Smith, Brandon W; Williamson, Craig A; Park, Paul

    2016-08-01

    Nontraumatic subdural hematoma (NTSDH) is a common neurosurgical disease process, with mortality reported as high as 13%. Seizure has a known association with NTSDH, although patient outcomes have not previously been well studied in this population. The purpose of this study was to examine the relationship between in-hospital seizure and inpatient outcomes in NTSDH. Using the University HealthSystem Consortium (UHC) database, we performed a retrospective cohort study of adults with a principal diagnosis of NTSDH (International Classification of Diseases, Ninth Revision code 43.21) between 2011 and 2015. Patients with in-hospital seizure (International Classification of Diseases, Ninth Revision codes 34500-34591, 78033, 78039) were compared with those without. Patients with a history of seizure before arrival were excluded. Patient demographics, hospital length of stay (LOS), intensive care unit stay, in-hospital mortality, and direct costs were recorded. A total 16,928 patients with NTSDH were identified. Mean age was 69.2 years, and 64.7% were male. In-hospital seizure was documented in 744 (4.40%) patients. Hospital LOS was 17.64 days in patients with seizure and 6.26 days in those without (P stay increased from 3.36 days without seizure to 9.36 days with seizure. In-hospital mortality was 9.19% in patients without seizure and 16.13% in those with seizure (P < 0.0001). Direct costs were $12,781 in patients without seizure and $38,110 in those with seizure (P < 0.0001). Seizure in patients with NTSDH correlates with significantly increased total LOS and increased mortality. Direct costs are similarly increased. Further studies accounting for effects of illness severity are necessary to validate these results. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Prognosis of patients in coma after acute subdural hematoma due to ruptured intracranial aneurysm.

    Science.gov (United States)

    Torné, Ramon; Rodríguez-Hernández, Ana; Romero-Chala, Fabián; Arikan, Fuat; Vilalta, Jordi; Sahuquillo, Juan

    2016-04-01

    Acute subdural hematomas (aSDH) secondary to intracranial aneurysm rupture are rare. Most patients present with coma and their functional prognosis has been classically considered to be very poor. Previous studies mixed good-grade and poor-grade patients and reported variable outcomes. We reviewed our experience by focusing on patients in coma only and hypothesized that aSDH might worsen initial mortality but not long-term functional outcome. Between 2005 and 2013, 440 subarachnoid hemorrhage (SAH) patients were admitted to our center. Nineteen (4.3%) were found to have an associated aSDH and 13 (2.9%) of these presented with coma. Their prospectively collected clinical and outcome data were reviewed and compared with that of 104 SAH patients without aSDH who presented with coma during the same period. Median aSDH thickness was 10mm. Four patients presented with an associated aneurysmal cortical laceration and only one had good recovery. Overall, we observed good long-term outcomes in both SAH patients in coma with aSDH and those without aSDH (38.5% versus 26.4%). Associated aSDH does not appear to indicate a poorer long-term functional prognosis in SAH patients presenting with coma. Anisocoria and brain herniation are observed in patients with aSDH thicknesses that are smaller than those observed in trauma patients. Despite a high initial mortality, early surgery to remove the aSDH results in a good outcome in over 60% of survivors. Aneurysmal cortical laceration appears to be an independent entity which shows a poorer prognosis than other types of aneurysmal aSDH. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The Risk Factors for Hydrocephalus and Subdural Hygroma after Decompressive Craniectomy in Head Injured Patients.

    Science.gov (United States)

    Ki, Hee Jong; Lee, Hyung-Jin; Lee, Hong-Jae; Yi, Jin-Seok; Yang, Ji-Ho; Lee, Il-Woo

    2015-09-01

    The present study aims to investigate 1) the risk factors for hydrocephalus and subdural hygroma (SDG) occurring after decompressive craniectomy (DC), and 2) the association between the type of SDG and hydrocephalus. We retrospectively reviewed the clinical and radiological features of 92 patients who underwent DC procedures after severe head injuries. The risk factors for developing post-traumatic hydrocephalus (PTH) and SDG were analyzed. Types of SDGs were classified according to location and their relationship with hydrocephalus was investigated. Ultimately, 26.09% (24/92) of these patients developed PTH. In the univariate analyses, hydrocephalus was statically associated with large bone flap diameter, large craniectomy area, bilateral craniectomy, intraventricular hemorrhage, contralateral or interhemisheric SDGs, and delayed cranioplasty. However, in the multivariate analysis, only large craniectomy area (adjusted OR=4.66; p=0.0239) and contralateral SDG (adjusted OR=6.62; p=0.0105) were significant independent risk factors for developing hydrocephalus after DC. The incidence of overall SDGs after DC was 55.43% (51/92). Subgroup analysis results were separated by SDG types. Statistically significant associations between hydrocephalus were found in multivariate analysis in the contralateral (adjusted OR=5.58; p=0.0074) and interhemispheric (adjusted OR=17.63; p=0.0113) types. For patients who are subjected to DC following severe head trauma, hydrocephalus is associated with a large craniectomy area and contralateral SDG. For SDGs after DC that occur on the interhemispherical or controlateral side of the craniectomy, careful follow-up monitoring for the potential progression into hydrocephalus is needed.

  9. High programmed cell death 1 ligand-1 expression: association with CD8+ T-cell infiltration and poor prognosis in human medulloblastoma.

    Science.gov (United States)

    Murata, Daiki; Mineharu, Yohei; Arakawa, Yoshiki; Liu, Bin; Tanji, Masahiro; Yamaguchi, Makoto; Fujimoto, Ko-Ichi; Fukui, Nobuyuki; Terada, Yukinori; Yokogawa, Ryuta; Yamaguchi, Maki; Minamiguchi, Sachiko; Miyamoto, Susumu

    2017-05-05

    OBJECTIVE Medulloblastoma is a type of malignant tumor arising in the cerebellum. The clinical importance of programmed cell death 1 ligand-1 (PD-L1) expression in medulloblastoma remains unknown. The aim of the present study was to examine the expression of PD-L1 and tumor-infiltrating T cells, and to evaluate their relationships to the prognosis of patients with medulloblastoma. METHODS The authors immunohistochemically analyzed PD-L1 expression and CD3+ and CD8+ lymphocyte infiltrations in tumor specimens from 16 patients with medulloblastoma. RESULTS High expression of PD-L1 was observed in 9 (56.3%) of 16 samples studied. High expression of PD-L1 was associated with low infiltrations of CD3+ or CD8+ lymphocytes. Patients with high expression of PD-L1 had shorter progression-free survival and overall survival times than those with low expression (p = 0.076 and p = 0.099, respectively). In addition, patients with high expression of PD-L1 and with low infiltration of CD8+ lymphocytes had a significantly worse outcome, with a 5-year survival rate of 15%, as compared with the other patients, who had a 5-year survival rate of nearly 90% (p = 0.0048 for progression-free survival and p = 0.010 for overall survival). CONCLUSIONS These findings indicate that PD-L1 expression was associated with a reduced infiltration of CD8+ T cells and poor prognosis in human medulloblastoma.

  10. Concurrent Intracranial and Spinal Subdural Hematoma in a Teenage Athlete: A Case Report of This Rare Entity

    Directory of Open Access Journals (Sweden)

    Daniel S. Treister

    2014-01-01

    Full Text Available A 15-year-old male high school football player presented with episodes of headache and complete body stiffness, especially in the arms, lower back, and thighs, immediately following a football game. This was accompanied by severe nausea and vomiting for several days. Viral meningitis was suspected by the primary clinician, and treatment with corticosteroids was initiated. Over the next several weeks, there was gradual symptom improvement and the patient returned to his baseline clinical status. The patient experienced a severe recurrence of the previous myriad of symptoms following a subsequent football game, without an obvious isolated traumatic episode. In addition, he experienced a new left sided headache, fatigue, and difficulty ambulating. He was admitted and an extensive workup was performed. CT and MRI of the head revealed concurrent intracranial and spinal subdural hematomas (SDH. Clinical workup did not reveal any evidence of coagulopathy or predisposing vascular lesions. Spinal SDH is an uncommon condition whose concurrence with intracranial SDH is an even greater clinical rarity. We suggest that our case represents an acute on chronic intracranial SDH with rebleeding, membrane rupture, and symptomatic redistribution of hematoma to the spinal subdural space.

  11. Does hypernatremia cause subdural hematoma in children?: two case reports and a meta-analysis of the literature.

    Science.gov (United States)

    Ali, Syed Adnaan; Jaspan, Timothy; Marenah, Christine; Vyas, Harish

    2012-06-01

    Hypernatremia has been causally linked with subdural hematoma (SDH), but more recently this has been called into question. Conversely, there is a well-established link between SDH and injury. We wish to examine the evidence base that hypernatremia in infants and young children causes SDH.We present 2 cases of children with severe hypernatremia whose intracranial contents were assessed by imaging in the first case and postmortem examination in the second. Neither demonstrated SDH. The first case was important as the hypernatremia was iatrogenic occurring in a controlled hospital environment.We also searched the literature from 1950 to 2007, collecting data on all reported cases of hypernatremia in children younger than 7 years whose intracranial contents were examined by imaging, surgery, and/or postmortem examination. Of 124 cases reported in 31 articles, 112 cases developed hypernatremia in the community, and 12 in the hospital. Subdural hematoma was demonstrated in 7 cases, all of which had developed hypernatremia in the community under circumstances that would make it difficult to exclude nonaccidental injury. None of the 12 cases that developed hypernatremia in a controlled hospital environment had SDH.The evidence base supporting the hypothesis that hypernatremia causes SDH is poor, depending on isolated reports with uncertain histories.

  12. Pola Kejadian Hematoma Subdural Pada Bayi Yang dirawat di Ruang Rawat Intensif Anak Rumah Sakit Dr. Hasan Sadikin

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    Enny Harliany Alwi

    2009-09-01

    Full Text Available Subdural hematoma (SDH is a common condition in infancy and young children with a poor prognostic. The more studies related SDH with nonaccidental injury. With the aim to identify the characteristics of SDH in infants below 1 year, a retrospective study of infants below 1 year diagnosed as subdural hematoma who were admitted to PICU Hasan Sadikin General Hospital from Januari 2000 to Desember 2003 has been conducted. Infants less than 1 month and SDH developed after neurosurgery intervention were excluded. Fourteen infants met the inclusion criteria's, consisted of 5 (36% girls and 9 (64% boys, most of them were on 1 month of age (57%. Anemia was found on all cases, thrombocyte normal except in 1 case thrombocytopenia (53,000/mm3. PT prolonged in 9 (100% cases and PTT in 5 (56% from 9 cases. Bilirubin total/direct elevated in 4 (80% from 5 cases, SGOT/SGPT elevated in 5 (83% from 6 cases. From 11 cases, 9 (82% cases were IgG anti-CMV positive and 6 (55% cases were IgM anti CMV positive. Conclusions, SDH can be caused by various etiologies, thus a comprehensive examinations to exclude child abuse are needed. The role of CMV infection should be considered as one of SDH etiology.

  13. Acute Subdural Hematoma and Subarachnoid Hemorrhage Caused by Ruptured Cortical Artery Aneurysm: Case Report and Review of Literature

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    Ahmad Shekarchizadeh

    2017-01-01

    Full Text Available The present report describes an acute subdural hematoma (ASDH associated with subarachnoid hemorrhage (SAH, due to ruptured cortical aneurysm. To our knowledge, extremely rare cases of this sort have been reported so far. A 23-year-old male patient without previous trauma presented with severe headache and rapidly decreasing level of consciousness to decerebrate status. Computed tomography (CT scan has demonstrated an ASDH together with SAH. Hematoma has immediately been evacuated without any evaluation by angiography. After evacuation of the thick subdural clot, a 10-mm aneurysm was revealed on a precentral artery of frontal cortex, which was ligated. However, after 35 days the patient discharged with left side hemiparesis and dysphasia, and just after several months of admission he got symptom free. Ruptured cortical aneurysm should be considered as one of the causes of spontaneous ASDH. Vascular anomaly investigations are suggested for these cases, thus CT angiography or digital subtraction angiography has to be considered if clinical condition allows.

  14. Life-threatening subdural hematoma after aortic valve replacement in a patient with Heyde syndrome: a case report.

    Science.gov (United States)

    Uchida, Tetsuro; Hamasaki, Azumi; Ohba, Eiichi; Yamashita, Atsushi; Hayashi, Jun; Sadahiro, Mitsuaki

    2017-08-08

    Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare. A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation. Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

  15. Chronic subdural hematoma of the posterior fossa associated with cerebellar hemorrhage: report of rare disease with MRI findings Hematoma subdural crônico de fossa posterior associado a hemorragia cerebelar espontânea: relato de doença rara com achados de RNM

    Directory of Open Access Journals (Sweden)

    Leodante B. Costa Jr

    2004-03-01

    Full Text Available Chronic subdural hematoma of the posterior fossa is an uncommon entity, and spontaneous lesions are very rarely described, occurring mostly during anticoagulation therapy. The association of the posterior fossa chronic subdural hematoma with spontaneous parenchymal hemorrhage without anticoagulation therapy was never related in the literature, to our knowledge. We describe a case of a 64 year-old woman who suffered a spontaneous cerebellar hemorrhage, treated conservatively, and presented 1 month later with a chronic subdural posterior fossa hematoma.Hematomas subdurais da fossa posterior são lesões raras, mais comumente relacionadas com traumas graves. A ocorrência de hematomas subdurais crônicos na fossa posterior é muito rara, sendo descritos 15 casos até o momento, boa parte relacionada ao uso de anticoagulantes. Em nossa revisão da literatura, não pudemos encontrar nenhum relato da associação entre hematoma subdural crônico da fossa posterior e hemorragia cerebelar espontânea. Relatamos o caso de paciente de 64 anos com hematoma intraparenquimatoso cerebelar tratado conservadoramente e hematoma subdural crônico, tratado cirurgicamente, cerca de 1 mês após o acidente vascular cerebelar.

  16. Combined radiotherapy and chemotherapy for pediatric medulloblastoma: a clinical study of 33 cases

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    Wei ZHENG

    2011-06-01

    Full Text Available Objective To retrospectively review the clinical characteristics of medulloblastoma,discuss the optimized treatment regimen,and analyze the prognostic influential factors.Methods Thirty-three children with pathologically certified medulloblastoma(aged 3-14 years with average of 6.5 years,admitted from Aug.2004 to Dec.2007,received radiotherapy within 3 weeks post surgery.Ratiotherapy consisted of 28~36Gy whole craniospinal radiation and a supplementary radiation aimed at tumors by three-dimensional conformal radiotherapy(3D-CRT for a total dose of 50~54Gy(conventional fraction dose of 1.8-2.0Gy.A part of patients received hyperfractionation radiotherapy(1.0Gy/f,2f/d for alleviating the tardive adverse events.Meanwhile,a synchronized chemotherapy,consisting of lomustine + vincristine + cisplatin,or isophosphamide + carboplatin + etoposide,was administered after the completion of whole craniospinal radiation,and 3-5 courses of sequential chemotherapy were given after the overall radiotherapy was finished.According to the metastasis,and the residual tumor and its size,the 33 patients were divided into 2 groups as follows: low-risk group(n=24: no metastases,total or sub-total excision of tumors(residual tumors ≤1.5cm3;high-risk group(n=9: either metastases or residual tumor > 1.5cm3.The 3-year survival rates of two groups were then compared.Results The combined radiotherapy and chemotherapy was effective to 10 of the 11 patients(90.9% with residual tumors.Out of the 33 patients,31 obtained complete remission(93.9%,and 2 patients showed partial remission or stable status(3.0%,respectively.The median survival time of 33 patients was 51 months,3-year disease free survival(DFS was 75.8%,and 3-year overall survival(OS was 78.8%,including 33.3% in high-risk group and 95.8% in low-risk group(P < 0.01.The major side effects occurred in haematological system and digestive system,such as an incidence of 21.2%(7/33 with grade Ⅲ-Ⅳ bone marrow suppression

  17. Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

    Science.gov (United States)

    Pols, San Y C V; van Veelen, Marie Lise C; Aarsen, Femke K; Gonzalez Candel, Antonia; Catsman-Berrevoets, Coriene E

    2017-07-01

    OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the

  18. A male infant had subdural effusion and paroxysmal supraventricular tachycardia during the febrile episode of Kawasaki disease: a case report and literature review.

    Science.gov (United States)

    Chou, Chia-Pei; Lin, I-Chun; Kuo, Kuang-Che

    2016-05-28

    Kawasaki disease is an acute, febrile, self-limiting, inflammatory systemic vasculitis seen in early childhood, most commonly in those below 5 years of age. In Kawasaki disease, the coronary arteries are most commonly affected, which may lead to asymptomatic coronary artery ectasia or formation of an aneurysm. Paroxysmal supraventricular tachycardia(PSVT) is a severe and rare cardiovascular complication of Kawasaki disease. A case of Kawasaki disease presenting with unusual findings, including subdural effusion and PSVT is reported. This is a 4-month-10-day-old boy presents with anterior fontanelle bulging and moderate bilateral subdural effusion at the acute stage of Kawasaki disease and PSVT at the subacute stage of Kawasaki disease. The subdural effusion was resolution after intravenous immunoglobulin(IVIG) administration. And the PSVT was subsided after administered 3 doses of adenosine, 1 dose of amiodarone loading and Propranolol twice per day use. At 1-year follow-up has made a complete recovery with no arrhythmia episodes, developmental effects or abnormal neurologic findings. Subdural effusion in the acute stage of Kawasaki disease may be an inflammatory response. It may resolves spontaneously after anti-inflammatory treatment such as IVIG infusion. PSVT is a severe cardiovascular complication of Kawasaki disease. In those who taking aspirin, we need to carefully observe the heart rhythm and PSVT side effects, especially in the first month.

  19. Analysis of the causes of subfrontal recurrence in medulloblastoma and its salvage treatment

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    Cho, Jae Ho; Koom, Woong Sub; Lee, Chang Geol [Yonsei University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2004-09-15

    Firstly, to analyze factors in terms of radiation treatment that might potentially cause subfrontal replace in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma. Secondly, to explore an effective salvage treatment for these relapses. Two patients who had high-risk disease (T3bM1, T3bM3) were treated with combined chemoradiotherapy. CT-simulation based radiation-treatment planning (RTP) was performed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. Review of radiotherapy portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume. When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who

  20. Subdural hematoma (SDH): assessment of macrophage reactivity within the dura mater and underlying hematoma.

    Science.gov (United States)

    Al-Sarraj, S; Mohamed, S; Kibble, M; Rezaie, P

    2004-01-01

    Macrophages are an inherent component of the dura mater, and can be characterised in cases of subdural hematoma (SDH) by their progressive and varying accumulation within areas of damage. Gross and histological methods used to determine the age of SDH are inexact. These are in part due to the active nature of such lesions and the diverse manner in which trauma victims respond to injury. Correct diagnosis has obvious medico-legal implications. However, there is as yet no specific diagnostic method that allows the age of SDH to be reliably determined. This study investigated the progressive and orderly pattern of reactivity of resident and infiltrating dural macrophages that occurs in response to injury associated with SDH. 26 postmortem cases of traumatic SDH were examined with survival times (onset of trauma to death) ranging from a few hours and up to 31 days. Macrophage reactivity associated with the dura mater and the underlying hematoma was determined using CD68 and MHC class II immunohistochemistry and the qualitative and quantitative findings compared with the presence of iron detected using conventional Perl's Prussian blue method. The results show that CD68 and MHC class II are differentially expressed within the dura mater and hematoma in SDH, and that the expression of MHC class II is markedly upregulated in the inner aspect of the dura mater within the initial 24 hours following injury. CD68 expression can be detected quantitatively in the hematoma, 24-48 hours after SDH, and within the dura following this period. Linear regression analysis further revealed a significant and positive association between the expression of MHC class II or CD68 antigens and the progressive survival of SDH up to 31 days post-injury, which was not seen with Perl's histochemical method. The expression of MHC class II antigen was a distinguishing, and quantifiable feature particularly localized within the inner aspect of the dura from a very early stage in the progression of

  1. Mathematical formulae to estimate chronic subdural haematoma volume. Flawed assumption regarding ellipsoid morphology.

    Science.gov (United States)

    Manickam, Appukutty; Marshman, Laurence A G; Johnston, Ross; Thomas, Piers A W

    2017-06-01

    Mathematical formulae are commonly used to estimate intra-cranial haematoma volume. Such formulae tacitly assume an ellipsoid geometrical morphology. Recently, the 'XYZ/2' formula has been validated and recommended for chronic subdural haematoma (CSDH) volumetric estimation. We aimed to assess the precision and accuracy of mathematical formulae specifically in estimating CSDH volume, and to determine typical CSDH 3-D morphology. Three extant formulae ('XYZ/2', 'π/6·XYZ' and '2/3S·h') were compared against computer-assisted 3D volumetric analysis as Gold standard in CTs where CSDH sufficiently contrasted with brain. Scatter-plots (n=45) indicated that, in contrast to prior reports, all formulae most commonly over-estimated CSDH volume against 3-D Gold standard ('2/3S·h': 44.4%, 'XYZ/2': 48.84% and 'π/6·XYZ': 55.6%). With all formulae, imprecision increased with increased CSDH volume: in particular, with clinically-relevant CSDH volumes (i.e. >50ml). Deviations >10% of equivalence were observed in 60% of estimates for 2/3S·h, 77.8% for 'XYZ/2' and 84.4% for 'π/6·XYZ'. The maximum error for 'XYZ/2' was 142.3% of a clinically-relevant volume. Three-D simulations revealed that only 4/45 (9%) CSDH remotely conformed to ellipsoid geometrical morphology. Most (41/45, 91%) demonstrated highly irregular morphology neither recognisable as ellipsoid, nor as any other regular/non-regular geometric solid. Mathematical formulae, including 'XYZ/2', most commonly proved inaccurate and imprecise when applied to CSDH. In contrast to prior studies, all most commonly over-estimated CSDH volume. Imprecision increased with CSDH volume, and was maximal with clinically-relevant CSDH volumes. Errors most commonly related to a flawed assumption regarding ellipsoid 3-D CSDH morphology. The validity of mean comparisons, or correlation analyses, used in prior studies is questioned. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  2. Medulloblastoma with extensive nodularity - imaging findings of a rare variant: a case report; Meduloblastoma nodular - achados de imagem de uma rara variante: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Santa Anna, Tatiana Kelly Brasileiro de; Zuppani, Aguinaldo Cunha [Hospital Santa Marcelina, Sao Paulo, SP (Brazil). Setor de Radiologia e Diagnostico por Imagem], e-mail: tatianakelly@hotmail.com; Neves, Izanne Martins; Trad, Clovis Simao [Clinica CEDIRP, Ribeirao Preto, SP (Brazil); Rigueiro, Moacyr Pezati

    2009-01-15

    Medulloblastoma is the most common malignant central nervous system tumor in pediatric patients and the most common primary tumor in the posterior fossa in children, most manifest in patients 5-12 years of age. Clinical features are mainly characterized by intracranial hypertension and ataxia. The authors present a case of medulloblastoma with extensive nodularity, a rare variant which affects younger age usually under three years, with more favorable prognosis. It is typically a cystic lesion in the posterior fossa with solid nodular components that enhance after contrast, like 'bunch of grapes' clusters. Preoperative diagnosis could be suggested by this finding. (author)

  3. Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype.

    Science.gov (United States)

    Castro-Gamero, Angel Mauricio; Borges, Kleiton Silva; Lira, Regia Caroline; Andrade, Augusto Faria; Fedatto, Paola Fernanda; Cruzeiro, Gustavo Alencastro Veiga; Silva, Ricardo Bonfim; Fontes, Aparecida Maria; Valera, Elvis Terci; Bobola, Michael; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga

    2013-10-01

    Chromosomal heterogeneity is a hallmark of most tumors and it can drive critical events as growth advantages, survival advantages, progression and karyotypic evolution. Medulloblastoma (MB) is the most common malignant central nervous system tumor in children. This work attempted to investigate chromosomal heterogeneity and instability profiles of two MB pediatric cell lines and their relationship with cell phenotype. We performed GTG-banding and cytokinesis-block micronucleus cytome assays, as well as morphological characterization, cell population doubling time, colony-forming efficiency, and chemo-sensitivity assays in two pediatric MB cell lines (UW402 and UW473). Both MB cells showed a high chromosomal heterogeneity. UW473 cells showed ~2 fold higher both clonal- and non-clonal chromosomal alterations than UW402 cells. Besides, UW473 showed two clonal-groups well-differentiated by ploidy level ( and ) and also presented a significantly higher number of chromosomal instability biomarkers. These results were associated with high morphological heterogeneity and survival advantages for UW473 and proliferation advantages for UW402 cells. Moreover, UW473 was significantly more sensitive to methotrexate, temozolomide and cisplatin while UW402 cells were more sensitive to doxorubicin. These data suggest that distinct different degrees of karyotypic heterogeneity and instability may affect neoplasic phenotype of MB cells. These findings bring new insights into cell and tumor biology.

  4. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

    Science.gov (United States)

    Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

    2015-01-01

    Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

  5. A visual latent semantic approach for automatic analysis and interpretation of anaplastic medulloblastoma virtual slides.

    Science.gov (United States)

    Cruz-Roa, Angel; González, Fabio; Galaro, Joseph; Judkins, Alexander R; Ellison, David; Baccon, Jennifer; Madabhushi, Anant; Romero, Eduardo

    2012-01-01

    A method for automatic analysis and interpretation of histopathology images is presented. The method uses a representation of the image data set based on bag of features histograms built from visual dictionary of Haar-based patches and a novel visual latent semantic strategy for characterizing the visual content of a set of images. One important contribution of the method is the provision of an interpretability layer, which is able to explain a particular classification by visually mapping the most important visual patterns associated with such classification. The method was evaluated on a challenging problem involving automated discrimination of medulloblastoma tumors based on image derived attributes from whole slide images as anaplastic or non-anaplastic. The data set comprised 10 labeled histopathological patient studies, 5 for anaplastic and 5 for non-anaplastic, where 750 square images cropped randomly from cancerous region from whole slide per study. The experimental results show that the new method is competitive in terms of classification accuracy achieving 0.87 in average.

  6. Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia.

    Science.gov (United States)

    Yamasaki, Fumiyuki; Takayasu, Takeshi; Nosaka, Ryo; Kawaguchi, Hiroshi; Sugiyama, Kazuhiko; Kobayashi, Masao; Kurisu, Kaoru

    2016-02-01

    While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. To our knowledge, this is the first report of AED-associated DNMB and CVA.

  7. Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in Medulloblastoma Daoy Cells.

    Science.gov (United States)

    Li, Chunhui; MacDonald, James I S; Talebian, Asghar; Leuenberger, Jennifer; Seah, Claudia; Pasternak, Stephen H; Michnick, Stephen W; Meakin, Susan O

    2016-10-15

    Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death. The molecular basis of this uncontrolled form of macropinocytosis has not been previously understood. Here, we demonstrate that the overactivation of macropinocytosis is caused by the simultaneous activation of two TrkA-mediated pathways: (i) inhibition of RhoB via phosphorylation at Ser(185) by casein kinase 1, which relieves actin stress fibers, and (ii) FRS2-scaffolded Src and H-Ras activation of RhoA, which stimulate actin reorganization and the formation of lamellipodia. Since catastrophic macropinocytosis results in brain tumor cell death, improved understanding of the mechanisms involved will facilitate future efforts to reprogram tumors, even those resistant to apoptosis, to die. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. A comparison of head dynamic response and brain tissue stress and strain using accident reconstructions for concussion, concussion with persistent postconcussive symptoms, and subdural hematoma.

    Science.gov (United States)

    Oeur, R Anna; Karton, Clara; Post, Andrew; Rousseau, Philippe; Hoshizaki, T Blaine; Marshall, Shawn; Brien, Susan E; Smith, Aynsley; Cusimano, Michael D; Gilchrist, Michael D

    2015-08-01

    Concussions typically resolve within several days, but in a few cases the symptoms last for a month or longer and are termed persistent postconcussive symptoms (PPCS). These persisting symptoms may also be associated with more serious brain trauma similar to subdural hematoma (SDH). The objective of this study was to investigate the head dynamic and brain tissue responses of injury reconstructions resulting in concussion, PPCS, and SDH. Reconstruction cases were obtained from sports medicine clinics and hospitals. All subjects received a direct blow to the head resulting in symptoms. Those symptoms that resolved in 9 days or fewer were defined as concussions (n = 3). Those with symptoms lasting longer than 18 months were defined as PPCS (n = 3), and 3 patients presented with SDHs (n = 3). A Hybrid III headform was used in reconstruction to obtain linear and rotational accelerations of the head. These dynamic response data were then input into the University College Dublin Brain Trauma Model to calculate maximum principal strain and von Mises stress. A Kruskal-Wallis test followed by Tukey post hoc tests were used to compare head dynamic and brain tissue responses between injury groups. Statistical significance was set at p concussion group (149 g and 8111 rad/sec(2), respectively; p brain tissue measures of maximum principal strain or von Mises stress. The reconstruction of accidents resulting in a concussion with transient symptoms (low severity) and SDHs revealed a positive relationship between an increase in head dynamic response and the risk for more serious brain injury. This type of relationship was not found for brain tissue stress and strain results derived by finite element analysis. Future research should be undertaken using a larger sample size to confirm these initial findings. Understanding the relationship between the head dynamic and brain tissue response and the nature of the injury provides important information for developing strategies for injury

  9. Treatment of chronic subdural hematomas with subdural evacuating port system placement in the intensive care unit: evolution of practice and comparison with bur hole evacuation in the operating room.

    Science.gov (United States)

    Flint, Alexander C; Chan, Sheila L; Rao, Vivek A; Efron, Allen D; Kalani, Maziyar A; Sheridan, William F

    2017-12-01

    OBJECTIVE The aims of this study were to evaluate a multiyear experience with subdural evacuating port system (SEPS) placement for chronic subdural hematoma (cSDH) in the intensive care unit at a tertiary neurosurgical center and to compare SEPS placement with bur hole evacuation in the operating room. METHODS All cases of cSDH evacuation were captured over a 7-year period at a tertiary neurosurgical center within an integrated health care delivery system. The authors compared the performance characteristics of SEPS and bur hole placement with respect to recurrence rates, change in recurrence rates over time, complications, length of stay, discharge disposition, and mortality rates. RESULTS A total of 371 SEPS cases and 659 bur hole cases were performed (n = 1030). The use of bedside SEPS placement for cSDH treatment increased over the 7-year period, from 14% to 80% of cases. Reoperation within 6 months was higher for the SEPS (15.6%) than for bur hole drainage (9.1%) across the full 7-year period (p = 0.002). This observed overall difference was due to a higher rate of reoperation during the same hospitalization (7.0% for SEPS vs 3.2% for bur hole; p = 0.008). Over time, as the SEPS procedure became more common and modifications of the SEPS technique were introduced, the rate of in-hospital reoperation after SEPS decreased to 3.3% (p = 0.02 for trend), and the difference between SEPS and bur hole recurrence was no longer significant (p = 0.70). Complications were uncommon and were similar between the groups. CONCLUSIONS Overall performance characteristics of bedside SEPS and bur hole drainage in the operating room were similar. Modifications to the SEPS technique over time were associated with a reduced reoperation rate.

  10. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Tejpal, E-mail: tejpalgupta@rediffmail.com [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Jalali, Rakesh [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Goswami, Savita [Department of Clinical Psychology and Psychiatry Unit, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Nair, Vimoj [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Moiyadi, Aliasgar [Division of Neuro-Surgery, Department of Surgical Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Epari, Sridhar [Department of Pathology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Sarin, Rajiv [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India)

    2012-08-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children {>=}5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  11. Proton radiation therapy for pediatric medulloblastoma and supratentorial primitive neuroectodermal tumors: outcomes for very young children treated with upfront chemotherapy.

    Science.gov (United States)

    Jimenez, Rachel B; Sethi, Roshan; Depauw, Nicolas; Pulsifer, Margaret B; Adams, Judith; McBride, Sean M; Ebb, David; Fullerton, Barbara C; Tarbell, Nancy J; Yock, Torunn I; Macdonald, Shannon M

    2013-09-01

    To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). All patients aged chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The postirradiation incidence of cavernous angioma is higher in patients with childhood pineoblastoma or primitive neuroectodermal tumors than medulloblastoma.

    Science.gov (United States)

    Yamasaki, Fumiyuki; Takayasu, Takeshi; Nosaka, Ryo; Kenjo, Masahiro; Akiyama, Yuji; Tominaga, Atsushi; Sugiyama, Kazuhiko; Kobayashi, Masao; Kurisu, Kaoru

    2015-06-01

    The purpose of this study is to investigate the incidence of cavernous angioma (CVA) in long-term survivors of childhood embryonal tumors treated by cranial irradiation. Between 1990 and 2012, we treated 25 patients (13 males, 12 females) with embryonal tumors (17 medulloblastomas, 5 primitive neuroectodermal tumors (PNET), 3 pineoblastomas) with craniospinal irradiation. Follow-up ranged from 15.5 to 289.9 months, the irradiation dose to the whole neural axis from 18 to 36 Gy, and the total local dose from 49.6 to 60 Gy. All patients underwent follow-up magnetic resonance imaging (MRI) studies at least once a year, and the diagnosis of posttreatment CVA was based solely on MRI findings. At the time of this writing, 18 were alive and free of the recurrence of the original disease or the development of secondary neoplasms other than CVA; another 2 were alive with medulloblastoma or diffuse astrocytoma. Posttreatment, 14 patients developed CVAs in the course of a median of 56.7 months; 13 of these presented with multiple CVAs. Patients who underwent radia